Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 84 Records) |
Query Trace: Raphael B [original query] |
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SARS-CoV-2, Mannerism, Marten, Mink, and Man
Swancutt M , Chorba T . Emerg Infect Dis 2021 27 (7) 2003-2005 Girolamo Francesco Maria Mazzola (1503–1540), known as Parmigianino (the little one from Parma), was a painter and printmaker. He was born into a family of painters in Parma, in what was then the Duchy of Milan, and died in Cremona, in northern Italy. He was among the first and most prominent artists of the Mannerist school of art of the Late Renaissance that came after the High Renaissance. The High Renaissance is known for the works of Raphael and the early works of Michelangelo, and its art is treasured for perfection of elegance and qualities of balance, proportion, and absoluast, in Mannerism, compositions are said to be exaggerated, almost to a fault, as a reaction to the art of the High Renaissance or perhaps as an attempt to improve on it. In general, it is characterized by realist but decorous art in which there is subtle, unsettling elongation of figures with stylized features and poses. | | Among Parmigianino’s more renowned works is a portrait painting from 1531‒1534 of a young woman, Antea, which appears on the cover of this month’s journal. It is unknown if the painting is an image of a specific person or a stylized composition. We behold a beautiful young woman facing forward, with elongated bodily proportions, as is characteristic of Mannerist works. With a small oval head set upon a large torso and with wide shoulders, her arms and hands appear exaggerated in size, as if the parts of her body were proportioned for different paintings. Yet despite these physical disproportions, the viewer has an impression of great beauty, a testimony to the subtlety and success of this Mannerist portrait. Contributing to the incongruousness of the image of this young lady, we also note that she is clad in the garments of an older woman, or a woman of an age with which we more commonly associate wealth; Antea is bejeweled, fingering a gold chain with her left hand, and dressed luxuriously. Among her layers of garments are a gold blouse with a fine white apron, a detailed gold satin dress, leather gloves, and a marten fur stole complete with the animal’s head, on which the nose is pierced with a ring still attached to a chain. |
Notes from the field: Locally acquired mosquito-transmitted (autochthonous) plasmodium falciparum malaria - national capital region, Maryland, August 2023
Duwell M , DeVita T , Torpey D , Chen J , Myers RA , Mace K , Ridpath AD , Odongo W , Raphael BH , Lenhart A , Tongren JE , Stanley S , Blythe D . MMWR Morb Mortal Wkly Rep 2023 72 (41) 1123-1125 Although malaria was eliminated in the United States in the mid-1950s, approximately 2,000 malaria cases are imported into the United States from regions with endemic disease transmission each year, including approximately 200 in Maryland* (Figure) (1). Anopheles mosquito species that can transmit malaria exist in many areas in the United States (2). Locally acquired mosquito-transmitted (i.e., autochthonous) cases have not been identified since 2003; however, these imported cases represent a potential source of infection. In mid-2023, eight autochthonous malaria cases (Plasmodium vivax) were identified in Florida and Texas (3); in both states, the autochthonous cases occurred in the vicinity of an imported malaria case. |
Outbreak of locally acquired mosquito-transmitted (autochthonous) malaria - Florida and Texas, May-July 2023
Blackburn D , Drennon M , Broussard K , Morrison AM , Stanek D , Sarney E , Ferracci C , Huard S , Brennan W , Eaton J , Nealeigh S , Barber N , Zimler RA , Adams JN , Blackmore C , Gordillo M , Mercado R , Vore H , Scanlan K , Motie I , Stanfield L , Farooq A , Widel K , Tomson K , Kerr N , Nasir J , Cone M , Rice C , Larkin T , Hernandez E , Bencie J , Lesser CR , Dersch M , Ramirez-Lachmann S , Clark M , Rollo S , Bashadi A , Tyler R , Bolling B , Moore B , Sullivan B , Fonken E , Castillo R , Gonzalez Y , Olivares G , Mace KE , Sayre D , Lenhart A , Sutcliffe A , Dotson E , Corredor C , Rogers E , Raphael BH , Sapp SGH , Qvarnstrom Y , Ridpath AD , McElroy PD . MMWR Morb Mortal Wkly Rep 2023 72 (36) 973-978 Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States. |
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. |
Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabs (preprint)
Bowden KE , Joseph SJ , Cartee JC , Ziklo N , Danavall D , Raphael BH , Read TD , Dean D . bioRxiv 2020 2020.09.04.282459 Chlamydia trachomatis is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. U.S. cases have been steadily increasing for more than a decade in both the urogenital tract and rectum. C. trachomatis is an obligate intracellular bacterium that is not easily cultured, limiting the capacity for genome studies to understand strain diversity and emergence among various patient populations globally. While Agilent SureSelectXT target-enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival and rectal samples, efficiencies are only 60-80% for ≥95-100% genome coverage. We therefore re-designed and expanded the RNA bait library to augment enrichment of the organism from clinical samples to improve efficiency. We describe the expanded library, the limit of detection for C. trachomatis genome copy input, and the 100% efficiency and high-resolution of generated genomes where genomic recombination among paired vaginal and rectal specimens from four patients was identified. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, among geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.Importance Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, and there is limited information on rectal C. trachomatis transmission and its impact on morbidity. To improve efficiency of previous studies involving whole genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we expanded the RNA bait library to augment enrichment of the organism from clinical samples. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis. We show the new system is sensitive for near identical genomes of C. trachomatis from two body sites in four women. Further, we provide a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital and rectal infections, and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity.Competing Interest StatementThe authors have declared no competing interest. |
Deer management generally reduces densities of nymphal Ixodes scapularis, but not prevalence of infection with Borrelia burgdorferi sensu stricto
Martin AM , Buttke D , Raphael J , Taylor K , Maes S , Parise CM , Ginsberg HS , Cross PC . Ticks Tick Borne Dis 2023 14 (5) 102202 Human Lyme disease-primarily caused by the bacterium Borrelia burgdorferi sensu stricto (s.s.) in North America-is the most common vector-borne disease in the United States. Research on risk mitigation strategies during the last three decades has emphasized methods to reduce densities of the primary vector in eastern North America, the blacklegged tick (Ixodes scapularis). Controlling white-tailed deer populations has been considered a potential method for reducing tick densities, as white-tailed deer are important hosts for blacklegged tick reproduction. However, the feasibility and efficacy of white-tailed deer management to impact acarological risk of encountering infected ticks (namely, density of host-seeking infected nymphs; DIN) is unclear. We investigated the effect of white-tailed deer density and management on the density of host-seeking nymphs and B. burgdorferi s.s. infection prevalence using surveillance data from eight national parks and park regions in the eastern United States from 2014-2022. We found that deer density was significantly positively correlated with the density of nymphs (nymph density increased by 49% with a 1 standard deviation increase in deer density) but was not strongly correlated with the prevalence of B. burgdorferi s.s. infection in nymphal ticks. Further, while white-tailed deer reduction efforts were followed by a decrease in the density of I. scapularis nymphs in parks, deer removal had variable effects on B. burgdorferi s.s. infection prevalence, with some parks experiencing slight declines and others slight increases in prevalence. Our findings suggest that managing white-tailed deer densities alone may not be effective in reducing DIN in all situations but may be a useful tool when implemented in integrated management regimes. |
Pandemic demand for SARS-CoV-2 testing led to critical supply and workforce shortages in U.S. clinical and public health laboratories
Cornish NE , Bachmann LH , Diekema DJ , McDonald LC , McNult P , Stevens-Garcia J , Raphael BH , Miller MB . J Clin Microbiol 2023 61 (7) e0318920 COVID-19 has brought unprecedented challenges to clinical and public health laboratories. While U.S. laboratories have continued striving to provide quality test results during the pandemic, the uncertainty and lack of supplies became a significant hurdle, hindering day-to-day laboratory operations and the ability to increase testing capacity for both SARS-CoV-2 and non-COVID-19 testing. In addition, long-standing laboratory workforce shortages became apparent, hindering the ability of clinical and public health laboratories to rapidly increase testing. The American Society for Microbiology, the College of American Pathologists, the National Coalition of STD Directors, and the Emerging Infections Network independently conducted surveys in 2020 and early 2021 to assess the capacity of the nation's clinical laboratories to respond to the increase in demand for testing during the COVID-19 pandemic. The results of these surveys highlighted the shortages of crucial supplies for SARS-CoV-2 testing and supplies for other routine laboratory diagnostics, as well as a shortage of trained personnel to perform testing. The conclusions are based on communications, observations, and the survey results of the clinical laboratory, public health, and professional organizations represented here. While the results of each survey considered separately may not be representative of the entire community, when considered together they provide remarkably similar results, further validating the findings and highlighting the importance of laboratory supply chains and the personnel capable of performing these tests for any response to a large-scale public health emergency. |
In vitro testing of Trichomonas vaginalis drug susceptibility: evaluation of minimal lethal concentrations for metronidazole and tinidazole that correspond with treatment failure
Augostini P , Bradley ELP , Raphael BH , Secor WE . Sex Transm Dis 2023 50 (6) 370-373 BACKGROUND: The only drugs approved by the U.S. Food and Drug Administration for oral treatment of trichomoniasis belong to the 5-nitroimidazole group. Most individuals infected with Trichomonas vaginalis can be cured with a standard treatment of metronidazole or tinidazole, but it is estimated that more than 159,000 people fail treatment each year. Although a minimal lethal concentration (MLC) corresponding to treatment failure has been reported for metronidazole, the MLC for tinidazole associated with treatment failure has not been determined. We conducted a study using T. vaginalis isolates from women with reported treatment success or failure to determine these values. METHODS: We measured MLCs of 47 isolates obtained from women who had failed metronidazole treatment, 33 isolates from women who had failed tinidazole treatment, and 48 isolates from women successfully cured with metronidazole. The cutoff was calculated as the 95th percentile of MLCs of susceptible isolates for each drug. RESULTS: Our data confirmed the MLC previously associated with metronidazole treatment failure is ≥50 μg/ml and identified the MLC associated with tinidazole treatment failure as ≥6.3 μg/ml. For metronidazole, the agreement between laboratory result and treatment outcome was 93.7%, for tinidazole this agreement was 88.9%. CONCLUSIONS: The T. vaginalis susceptibility assay is useful for determining whether 5-nitroimidazole treatment failure in persons with trichomoniasis can be attributed to drug resistance. These results are useful for establishing interpretive guidance of test results and MLC levels can help guide appropriate patient treatment. |
Community outbreak of legionellosis associated with an indoor hot tub, New Hampshire, 2018
Daly ER , Talbot EA , Smith JC , Ritter T , McCormic ZD , Fay K , Raphael BH , Kozak-Muiznieks NA , Levinson KJ , Bean CL , Wilson RT , Morse D , Scacheri A , Linxweiler J , Chan BP . J Environ Health 2022 84 (10) 16-25 Legionellosis is an infection acquired through inhalation of aerosolized water droplets containing Legionella bacteria. In August 2018, public health officials in New Hampshire launched an investigation into a legionellosis outbreak. They identified 49 illnesses likely associated with the outbreak and implicated an improperly maintained hot tub at a hotel. The same strain of Legionella pneumophila serogroup 1 was found in both the hot tub and in samples from two patients with Legionnaires disease. The indoor hot tub vented to the outdoors, which is how some patients with confirmed legionellosis likely acquired the infection despite not entering the hotel during the incubation period. This outbreak is notable for 1) likely illness acquisition through the exterior vent of the hot tub room and 2) use of whole genome sequencing to link environmental and patient specimens. Collaboration among public health and environmental officials, laboratorians, and building managers was essential to determining the source of the outbreak and preventing further illness. 2022, National Environmental Health Association. All rights reserved. |
Phylogenomic Comparison of Neisseria gonorrhoeae Causing Disseminated Gonococcal Infections and Uncomplicated Gonorrhea in Georgia, United States.
Cartee JC , Joseph SJ , Weston E , Pham CD , Thomas JCth , Schlanger K , St Cyr SB , Farley MM , Moore AE , Tunali AK , Cloud C , Raphael BH . Open Forum Infect Dis 2022 9 (7) ofac247 Disseminated gonococcal infection (DGI) is a rare complication caused by the systemic dissemination of Neisseria gonorrhoeae to normally sterile anatomical sites. Little is known about the genetic diversity of DGI gonococcal strains and how they relate to other gonococcal strains causing uncomplicated mucosal infections. We used whole genome sequencing to characterize DGI isolates (n = 30) collected from a surveillance system in Georgia, United States, during 2017-2020 to understand phylogenetic clustering among DGI as well as uncomplicated uro- and extragenital gonococcal infection (UGI) isolates (n = 110) collected in Fulton County, Georgia, during 2017-2019. We also investigated the presence or absence of genetic markers related to antimicrobial resistance (AMR) as well as surveyed the genomes for putative virulence genetic factors associated with normal human-serum (NHS) resistance that might facilitate DGI. We found that DGI strains demonstrated significant genetic variability similar to the population structure of isolates causing UGI, with sporadic incidences of geographically clustered DGI strains. DGI isolates contained various AMR markers and genetic mechanisms associated with NHS resistance. DGI isolates had a higher frequency of the porB1A allele compared with UGI (67% vs 9%, P < .0001); however, no single NHS resistance marker was found in all DGI isolates. Continued DGI surveillance with genome-based characterization of DGI isolates is necessary to better understand specific factors that promote systemic dissemination. |
Characterization of a Neisseria gonorrhoeae Ciprofloxacin panel for an antimicrobial resistant Isolate Bank.
Liu H , Tang K , Pham CD , Schmerer M , Kersh EN , Raphael BH . PLoS One 2022 17 (3) e0264149 OBJECTIVES: Neisseria gonorrhoeae (gonococcus) infection is one of the most commonly reported nationally notifiable conditions in the United States. Gonococcus has developed antimicrobial resistance to each previously used antibiotic for gonorrhea therapy. However, some isolates may be still susceptible to no longer recommended, yet still effective antibiotics. This in turn suggests that targeted therapy could slow resistance development to currently recommended empirical treatments. We curated a gonococcal Ciprofloxacin Antibiotic Resistance Isolate Bank panel (Cipro-panel) as a tool for validating or developing new tests to determine ciprofloxacin susceptibility. METHOD: The Cipro-panel was selected using whole genome sequencing, bioinformatic tools, and antimicrobial susceptibility testing (AST) data. Isolates were further selected based on nucleotide variations in gyrA and parC genes. RESULTS: We selected 14 unique N. gonorrhoeae isolates from the 2006-2012 Gonococcal Isolate Surveillance Project (GISP) collection. They represented a wide range of antimicrobial susceptibility to ciprofloxacin and commonly observed nucleotide variations of gyrA and parC genes. This Cipro-panel consists of 5 isolates with resistant phenotypes (MIC > = 1 g/mL), 8 isolates with susceptible phenotypes (MIC < = 0.06 g/mL), and 1 isolate falling in the Clinical and Laboratory Standards Institute defined intermediate range. Among the gyrA variations we observed a total of 18 SNPs. Four positions had nonsynonymous changes (nucleotide positions 272, 284, 1093, and 1783). The first two positions (272 and 284) have been linked previously with resistance to ciprofloxacin (i.e. amino acid positions 91 and 95). For the parC gene, we observed a total of 21 possible SNPs. Eight of those SNPs resulted in non-synonymous amino acid changes. One location (amino acid 87) has been previously reported to be associated with ciprofloxacin resistance. CONCLUSIONS: This Cipro-Panel is useful for researchers interested in developing clinical tests related to ciprofloxacin. It could also provide additional choices for validation, quality assurance purposes and improve antibiotic usage. |
Chlamydia trachomatis variants escaping detection in the Aptima Combo 2® assay in the United States.
Katz SS , Danavall DC , Morris MR , Herrod BP , Dale SE , Nye MB , Kersh EN , Kirkcaldy RD , Raphael BH . Sex Transm Dis 2022 49 (6) 448-452 BACKGROUND: The Aptima Combo 2 (AC2) assay manufactured by Hologic, Inc. detects Neisseria gonorrhoeae (NG) and/or Chlamydia trachomatis (CT) in urogenital and extragenital specimens by targeting either a 16S rRNA (NG) or 23S rRNA (CT) region. In 2019, a mutation (C1515T) in the 23S rRNA region was reported to cause false negative/equivocal results in specimens collected in Finland. Specimens containing this variant (Fl-nvCT) were also discovered internationally. Working with specimens submitted to a large commercial laboratory, we sought to determine if this variant was also present in the United States. METHODS: A subset (N = 401) of specimens tested with the AC2 assay collected during a five-week period in late 2019/early 2020 were evaluated using an updated AC2 assay. RESULTS: While the FI-nvCT variant was not detected within this specimen panel, two CT variants containing 23S rRNA mutations (A1518G, G1526A) were identified. The updated AC2 assay targeting an additional region of the 23S rRNA detected both of these variants. A retrospective study of >18 million AC2 results tested between 2018-2019 did not display a decrease in CT positivity. CONCLUSIONS: Although we did not detect the Fl-nvCT variant among US specimens, we show evidence that the low occurrence of similar diagnostic escape mutants can be detected with an updated AC2 assay using multiple 23S rRNA targets. |
Surveillance for disseminated gonococcal infections, Active Bacterial Core surveillance (ABCs) - United States, 2015-2019
Weston EJ , Heidenga BL , Farley MM , Tunali A , D'Angelo MT , Moore A , Workowski K , Raphael BH , Weinstock H , Torrone E . Clin Infect Dis 2022 75 (6) 953-958 BACKGROUND: Disseminated gonococcal infections (DGI) are thought to be uncommon; surveillance is limited and case reports are analyzed retrospectively or in case clusters. We describe the population-level burden of culture-confirmed DGI through the Active Bacterial Core surveillance (ABCs) system. METHODS: During 2015-2016, retrospective surveillance was conducted among residents in two ABCs areas and prospectively in three ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae (Ng) from a normally sterile site. A case report form was completed for each case and antimicrobial susceptibility testing (AST) was performed on available isolates. RESULTS: During 2015-2019, 77 DGI cases were identified (~a rate of 0.13 cases per 100,000 population) and accounted for 0.06% of all reported gonorrhea cases in the three surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16-67 years; blood (55%) and joint (40%) were the most common sterile sites. Among 29 isolates with AST results during 2017-2019, all were susceptible to ceftriaxone. CONCLUSIONS: DGI is an infrequent complication of Ng; since Ng can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations. |
Global emergence and dissemination of Neisseria gonorrhoeae ST-9363 isolates with reduced susceptibility to azithromycin.
Joseph SJ , Thomas Iv JC , Schmerer MW , Cartee J , St Cyr S , Schlanger K , Kersh EN , Raphael BH , Gernert KM . Genome Biol Evol 2021 14 (1) Neisseria gonorrhoeae multi-locus sequence type (ST) 9363 core-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 core-genogroup genomes to shed light on the emergence and dissemination of this strain. The global population structure of ST-9363 core-genogroup falls into three lineages: Basal, European, and North American; with 32 clades within all lineages. Although, ST-9363 core-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 core-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 core-genogroup, it remains critically important to continue monitoring it, as it could acquire additional resistance markers. |
Use of real-time PCR as an alternative to conventional genotyping methods for the laboratory detection of lymphogranuloma venereum (LGV).
Woodson EN , Katz SS , Mosley SS , Danavall DC , Bowden KE , Chi KH , Raphael BH . Diagn Microbiol Infect Dis 2021 101 (4) 115532 Lymphogranuloma venereum (LGV) can be differentiated from non-LGV chlamydial infection using Sanger sequencing or molecular assays, including those that are commercially-available internationally. Here, we describe the performance of a rapid real-time PCR (RT-PCR)-based strategy in differentiating Chlamydia trachomatis infections associated with LGV or non-LGV serovars. One hundred three rectal swabs, previously genotyped using Sanger sequencing of the ompA gene as a reference method, were tested in the RT-PCR assays. All non-LGV specimens were correctly identified, but the RT-PCR failed to detect 1 LGV specimen, resulting in a sensitivity of 87.5% for the non-LGV/LGV RT-PCR assay. Additional performance characteristics (e.g., specificity, accuracy, and reproducibility) were all between 93% and 100% with a limit of detection ≤100 copies/reaction. Thus, this rapid RT-PCR method for LGV detection in clinical specimens is comparable to the reference method. |
Impact of anatomic site, specimen collection timing, and patient symptom status on Neisseria gonorrhoeae culture recovery
Nash EE , Pham CD , Raphael B , Learner ER , Mauk K , Weiner J , Mettenbrink C , Thibault CS , Fukuda A , Dobre-Buonya O , Black JM , Johnson K , Sellers K , Schlanger K . Sex Transm Dis 2021 48 S151-S156 BACKGROUND: Neisseria gonorrhoeae culture is required for antimicrobial susceptibility testing (AST), but recovering isolates from clinical specimens is challenging. While many variables influence culture recovery, studies evaluating the impact of culture specimen collection timing and patient symptom status are limited. This study analyzed urogenital and extragenital culture recovery data from CDC's Strengthening US Response to Resistant Gonorrhea (SURRG) program, a multi-site project, which enhances local N. gonorrhoeae culture and AST capacity. METHODS: Eight SURRG jurisdictions collected gonococcal cultures from patients with N. gonorrhoeae-positive nucleic acid amplification tests (NAATs) attending STD and community clinics. Matched NAAT and culture specimens from the same anatomic site were collected, and culture recovery was assessed. Time between NAAT and culture specimen collection was categorized as, same day, 1-7 days, 8-14 days, or ≥ 15 days and patient symptoms were matched to the anatomic site where culture specimens were collected. RESULTS: From 2018-2019, among persons with N. gonorrhoeae-positive NAAT, urethral infections resulted in the highest culture recovery (5927/6515 = 91.0%), followed by endocervical, (222/363 = 61.2%), vaginal (63/133 = 47.4%) rectal (1117/2805 = 39.8%), and pharyngeal (1019/3678 = 27.7%) infections. Culture recovery was highest when specimens were collected on the same day as NAAT specimens and significantly decreased after 7 days. Symptoms were significantly associated with culture recovery at urethral (p = <0.0001) and rectal (p = <0.0001) sites of infection but not endocervical, vaginal, or pharyngeal sites. CONCLUSIONS: Culture specimen collection timing and patient symptomatic status can impact culture recovery. These findings can guide decisions about culture collection protocols to maximize culture recovery and strengthen detection of antimicrobial resistant infections. |
Implementation and evaluation of gradient strip antimicrobial susceptibility testing in US public health laboratories to respond to resistant gonorrhea
Raphael BH , Pham CD , Sharpe S , Mauk K , Harvey A , Khubbar M , Triplett L , Soge OO , Denny M , Palavecino EL , Finney R , Olsen A , Carlson J , St Cyr SB , Schlanger K , Kersh EN . Sex Transm Dis 2021 48 S157-S160 BACKGROUND: Gradient strip antimicrobial susceptibility testing (AST) using Etest® is conducted by local public health jurisdictions participating in the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) program to inform public health responses to resistant gonorrhea. Proficiency testing results across the participating laboratories were analyzed and a comparison of Etest® with the agar dilution method was conducted. METHODS: Laboratories participating in SURRG performed Etest® for azithromycin (AZM), cefixime (CFX), and ceftriaxone (CRO). Concurrence between minimum inhibitory concentrations (MICs) obtained with Etest® versus the agar dilution method using corresponding isolates was defined as +/- 1 double dilution. Specific levels of reduced susceptibility were termed "alerts" and included isolates with the following MICs: ≥ 2.0 μg/ml (AZM), ≥ 0.25 μg/ml (CFX), and ≥ 0.125 μg/ml (CRO). Categorical (alert/non-alert) agreement was calculated for MICs determined using Etest® and agar dilution methods. RESULTS: SURRG laboratories had high proficiency testing scores (≥98%) and low levels of inter-laboratory variations in MICs. The overall concurrence of MICs (essential agreement) determined using agar dilution and Etest® was 96% (CRO), 96% (CFX), and 95% (AZM). Depending on the antibiotic tested, between 27-66% of isolates with alert MICs determined by Etest® also had alert MICs using the reference agar dilution methodology, however most of these alert MICs were detected at threshold levels. CONCLUSIONS: This study demonstrates that MICs produced by SURRG laboratories using Etest® have a high level of concurrence with agar dilution. Although confirmation of specific alert MICs varied, Etest® facilities rapid detection and response to emerging resistant gonorrhea. |
Assessment and utility of 2 Chlamydia trachomatis Pgp3 serological assays for seroprevalence studies among women in the United States
Danavall DC , Gwyn S , Anyalechi GE , Bowden KE , Hong J , Kirkcaldy RD , Bernstein KT , Kersh EN , Martin D , Raphael BH . Diagn Microbiol Infect Dis 2021 101 (2) 115480 Two plasmid gene protein (Pgp3)-based serological assays, the Pgp3-ELISA and multiplex bead assay (Pgp3-MBA), were compared and used to estimate seropositivity of Chlamydia trachomatis (CT) among females 14 to 39 years old participating in the National Health and Nutrition Examination Survey between 2013-2016. Of the 2,201 specimens tested, 502 (29.5%, 95% CI 27.6-31.5) were positive using Pgp3-ELISA and 624 (28.4%, 95% CI 26.5-30.3) were positive using Pgp3-MBA. The overall agreement between the assays was 87.7%. Corresponding nucleic acid amplification test (NAAT) results were available for 1,725 specimens (from women 18-39 years old); of these, 42 (2.4%, 95% CI 1.8-3.3) were CT NAAT-positive. Most of the CT NAAT-positive specimens had corresponding positive serological assay results; 33 (78.6%, 95% CI 62.8-89.2) were Pgp3-ELISA-positive and 36 (85.7%, 95% CI 70.8-94.1) were Pgp3-MBA-positive. Although Pgp3-ELISA and Pgp3-MBA demonstrated equivalent performance in this study, an advantage of the Pgp3-MBA over Pgp3-ELISA is that it is well suited for high sample throughput applications. |
Exploring and comparing the structure of sexual networks affected by Neisseria gonorrhoeae using sexual partner services investigation and genomic data.
Town K , Learner ER , Chivukula VL , Mauk K , Reimche JL , Schmerer MW , Black J , Pathela P , Bhattacharyya S , Kerani RP , Gieseker KE , Fukuda A , Sankaran M , McNeil CJ , Spicknall IH , Raphael BH , St Cyr SB , Bernstein K , Kersh EN , Kirkcaldy RD , Schlanger K , Gernert KM . Sex Transm Dis 2021 48 S131-S136 BACKGROUND: Sexual networks are difficult to construct due to incomplete sexual partner data. The proximity of people within a network may be inferred from genetically similar infections. We explored genomic data combined with partner services investigation (PSI) data to extend our understanding of sexual networks affected by Neisseria gonorrhoeae (NG). METHODS: We used 2017-2019 PSI and whole-genome sequencing (WGS) data from eight jurisdictions participating in CDC's Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. Clusters were identified from sexual contacts and through genetically similar NG isolates. Sexual mixing patterns were characterized by describing the clusters by the individual's gender and gender of their sex partners. RESULTS: Our study included 4,627 diagnoses of NG infection (81% sequenced), 2,455 people received a PSI, 393 people were negative contacts of cases, and 495 contacts with unknown NG status. We identified 823 distinct clusters using PSI data combined with WGS data. Of cases that were not linked to any other case using PSI data, 37% were linked when using WGS data. Overall, 40% of PSI cases were allocated to a larger cluster when PSI and WGS data were combined compared with PSI data alone. Mixed clusters containing women, men who report sex with women, and men who report sex with men were common when using the WGS data either alone or in combination with the PSI data. CONCLUSIONS: Combining PSI and WGS data improves our understanding of sexual network connectivity. |
The Gombe Ecosystem Health Project: 16 years of program evolution and lessons learned
Lonsdorf EV , Travis DA , Raphael J , Kamenya S , Lipende I , Mwacha D , Collins DA , Wilson M , Mjungu D , Murray C , Bakuza J , Wolf TM , Parsons MB , Deere JR , Lantz E , Kinsel MJ , Santymire R , Pintea L , Terio KA , Hahn BH , Pusey AE , Goodall J , Gillespie TR . Am J Primatol 2021 84 e23300 Infectious disease outbreaks pose a significant threat to the conservation of chimpanzees (Pan troglodytes) and all threatened nonhuman primates. Characterizing and mitigating these threats to support the sustainability and welfare of wild populations is of the highest priority. In an attempt to understand and mitigate the risk of disease for the chimpanzees of Gombe National Park, Tanzania, we initiated a long-term health-monitoring program in 2004. While the initial focus was to expand the ongoing behavioral research on chimpanzees to include standardized data on clinical signs of health, it soon became evident that the scope of the project would ideally include diagnostic surveillance of pathogens for all primates (including people) and domestic animals, both within and surrounding the National Park. Integration of these data, along with in-depth post-mortem examinations, have allowed us to establish baseline health indicators to inform outbreak response. Here, we describe the development and expansion of the Gombe Ecosystem Health project, review major findings from the research and summarize the challenges and lessons learned over the past 16 years. We also highlight future directions and present the opportunities and challenges that remain when implementing studies of ecosystem health in a complex, multispecies environment. |
Phylogenomic analysis reveals persistence of gonococcal strains with reduced-susceptibility to extended-spectrum cephalosporins and mosaic penA-34.
Thomas 4th JC , Joseph SJ , Cartee JC , Pham CD , Schmerer MW , Schlanger K , St Cyr SB , Kersh EN , Raphael BH . Nat Commun 2021 12 (1) 3801 The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935-1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally. |
At-home Specimen Self-Collection and Self-Testing for STI Screening Demand Accelerated by the COVID-19 Pandemic - A Review of Laboratory Implementation Issues.
Kersh EN , Shukla M , Raphael BH , Habel M , Park I . J Clin Microbiol 2021 59 (11) Jcm0264620 The idea of specimen self-collection or self-STI testing is not new. In 2019, the World Health Organization (WHO) published the "WHO Consolidated Guideline on Self-Care Interventions for Health" as a first installment in a planned series for various diseases (8). The first document focused on "Sexual and Reproductive Health and Rights". Self-care including self-testing has the readily apparent benefits of privacy, confidentiality, speed, convenience, and access if the price is affordable. It is "people-centered" (9) and enables active participation in one's own health. It is also a health system approach as it can reduce burden on stretched systems with world-wide shortages in medical personnel or other barriers to health care access. Potential risks include: low specimen return rates, uncertain follow-up (linkage to care including treatment, repeat testing including test of cure, partner notification, counseling on risk reduction), unintended/unnecessary use (resulting in false positives with their own set of associated problems), incorrect use, lack of understanding of window periods (resulting in false negatives), lack of surveillance data generation, among other issues (9). The WHO systematically reviewed evidence for self-testing or specimen self-collection for GC, CT and syphilis, including US studies, and published a meta-analysis of available evidence (9). Programs offering self-collection of samples increased overall uptake of STI testing services (RR: 2.941, 95% CI 1.188 to 7.281) and case finding (RR: 2.166, 95% CI1.043 to 4.498), prior to the pandemic (9). U. S. laboratory research on the equivalence and/or superiority of self-collected versus provider-collected specimens for test sensitivity was reported by Gaydos et al (summarized or referenced in (10)). Based on this evidence, WHO issued a new recommendation in 2019 "Self-collection of samples for Neisseria gonorrhoeae and Chlamydia trachomatis should be made available as an additional approach to deliver STI testing services for individuals using STI testing services" (8). In addition, WHO issued a new and conditional recommendation: "Self-collection of samples for Treponema pallidum (syphilis) and Trichomonas vaginalis may be considered as an additional approach to deliver STI testing services for Individuals using STI testing services" (8). Thus, even before the COVID-19 pandemic, substantial expert agreement existed concerning benefits of this approach. |
High Pgp3 Chlamydia trachomatis seropositivity, pelvic inflammatory disease and infertility among women, National Health and Nutrition Examination Survey, United States, 2013-2016
Anyalechi GE , Hong J , Danavall DC , Martin DL , Gwyn SE , Horner PJ , Raphael BH , Kirkcaldy RD , Kersh EN , Bernstein KT . Clin Infect Dis 2021 73 (8) 1507-1516 BACKGROUND: Chlamydia trachomatis causes pelvic inflammatory disease (PID) and tubal infertility. Pgp3 antibody (Pgp3Ab) detects prior chlamydial infections. We evaluated for an association of high chlamydial seropositivity with sequelae using a Pgp3Ab multiplex bead array (Pgp3AbMBA). METHODS: We performed chlamydia Pgp3AbMBA on sera from women 18-39 years old participating in the 2013-2016 National Health and Nutrition Examination Survey (NHANES) with urine chlamydia nucleic acid amplification test results. High chlamydial seropositivity was defined as a median fluorescence intensity (MFI ≥ 50,000; low-positive was MFI > 551-<50,000. Weighted US population high-positive, low-positive, and negative Pgp3Ab chlamydia seroprevalence and 95% confidence intervals (95% CI) were compared for women with chlamydial infection, self-reported PID, and infertility. RESULTS: Of 2,339 women aged 18-39 years, 1,725 (73.7%) had sera and 1,425 were sexually experienced. Overall, 104 women had high positive Pgp3Ab (5.4% [95% CI 4.0-7.0] of US women); 407 had low positive Pgp3Ab (25.1% [95% CI 21.5-29.0]), and 914 had negative Pgp3Ab (69.5% [95% CI 65.5-73.4]).Among women with high Pgp3Ab, infertility prevalence was 2.0 (95% CI 1.1-3.7) times higher than among Pgp3Ab-negative women (19.6% [95% CI 10.5-31.7] versus 9.9% [95% CI 7.7-12.4]). For women with low Pgp3Ab, PID prevalence was 7.9% (95% CI 4.6-12.6) compared to 2.3% (95% CI 1.4-3.6) in negative Pgp3Ab. CONCLUSIONS: High chlamydial Pgp3Ab seropositivity was associated with infertility although small sample size limited evaluation of an association of high seropositivity with PID. In infertile women, Pgp3Ab may be a marker of prior chlamydial infection. |
Genomic analysis of the predominant strains and antimicrobial resistance determinants within 1479 Neisseria gonorrhoeae isolates from the U.S. Gonococcal Isolate Surveillance Project in 2018.
Reimche JL , Chivukula VL , Schmerer MW , Joseph SJ , Pham CD , Schlanger K , St Cyr SB , Weinstock HS , Raphael BH , Kersh EN , Gernert KM . Sex Transm Dis 2021 48 S78-S87 BACKGROUND: The prevalence of Neisseria gonorrhoeae (GC) isolates with elevated minimum inhibitory concentrations (MICs) to various antibiotics continues to rise in the U.S. and globally. Genomic analysis provides a powerful tool for surveillance of circulating strains, antimicrobial resistance determinants, and understanding of transmission through a population. METHODS: GC isolates collected from the U.S. Gonococcal Isolate Surveillance Project (GISP) in 2018 (n=1479) were sequenced and characterized. Whole genome sequencing was used to identify sequence types, antimicrobial resistance profiles, and phylogenetic relationships across demographic and geographic populations. RESULTS: Genetic characterization identified that (1) 80% of the GC isolates were represented in 33 multilocus sequence types, (2) isolates clustered in 23 major phylogenetic clusters with select phenotypic and demographic prevalence, and (3) common antimicrobial resistance determinants associated with low-level or high-level decreased susceptibility or resistance to relevant antibiotics. CONCLUSIONS: Characterization of this 2018 GISP genomic dataset, which is the largest U.S. whole genome sequence data set to date, sets the basis for future prospective studies, and establishes a genomic baseline of GC populations for local and national monitoring. |
2020 STD Prevention Conference: Disrupting Epidemics and Dismantling Disparities in the Time of COVID-19.
Raphael BH , Haderxhanaj L , Bowen VB . Sex Transm Dis 2021 48 S1-S3 The sexually transmitted disease (STD) Prevention Conference occurs every 2 years, bringing together experts from government, academia, medicine, industry, and beyond. This conference is a place where advancements in STD diagnostics, treatments, and program science are unveiled alongside earnest conversations about the prevention and control challenges facing the field of STDs in the 21st century. Planning for the 2020 Conference began in late 2018—organized around the theme “2020 Vision: Disrupting Epidemics and Dismantling Disparities.” The theme spoke both to an interest in reducing the overall STD burden and to an interest in reducing that burden in such a way that centers health equity—ambitious but reasonable goals for a new decade. |
A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch.
Sánchez-Busó L , Yeats CA , Taylor B , Goater RJ , Underwood A , Abudahab K , Argimón S , Ma KC , Mortimer TD , Golparian D , Cole MJ , Grad YH , Martin I , Raphael BH , Shafer WM , Town K , Wi T , Harris SR , Unemo M , Aanensen DM . Genome Med 2021 13 (1) 61 BACKGROUND: Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. METHODS: Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. RESULTS: AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. CONCLUSIONS: The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods. |
Insecticide Resistance Patterns and Mechanisms in Aedes aegypti (Diptera: Culicidae) Populations Across Abidjan, Côte d'Ivoire Reveal Emergent Pyrethroid Resistance.
Konan LY , Oumbouke WA , Silué UG , Coulibaly IZ , Ziogba JT , N'Guessan RK , Coulibaly D , Bénié JBV , Lenhart A . J Med Entomol 2021 58 (4) 1808-1816 From 2008 to 2017, the city of Abidjan, Côte d'Ivoire experienced several Aedes-borne disease epidemics which required control of the vector mosquito population based on the reduction of larval habitats and insecticidal sprays for adult mosquitoes. This study was undertaken to assess the insecticide susceptibility status of Aedes aegypti (Linnaeus) in the city of Abidjan. Immature Ae. aegypti were sampled from several larval habitats within seven communes of Abidjan and reared to adults. Three to five days old F1 emerged adults were tested for susceptibility using insecticide-impregnated papers and the synergist piperonyl butoxide (PBO) following WHO bioassay guidelines. The results showed that Ae. aegypti populations from Abidjan were resistant to 0.1% propoxur, and 1% fenitrothion, with mortality rates ranging from 0% to 54.2%. Reduced susceptibility (93.4-97.5% mortality) was observed to 0.05% deltamethrin, 0.75% permethrin, 0.05% lambda-cyhalothrin, 5% malathion, and 0.8% chlorpyrifos-methyl. This reduced susceptibility varied depending on the insecticide and the collection site. The restoration of mortality when the mosquitoes were pre-exposed to the synergist PBO suggests that increased activity of oxidases could be contributing to resistance. Three kdr mutations (V410L, V1016I, and F1534C) were present in populations tested, with low frequencies for the Leu410 (0.28) and Ile1016 (0.32) alleles and high frequencies for the Cys1534 allele (0.96). These findings will be used to inform future arbovirus vector control activities in Abidjan. |
Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabs.
Bowden KE , Joseph SJ , Cartee JC , Ziklo N , Danavall D , Raphael BH , Read TD , Dean D . mSphere 2021 6 (2) Chlamydia trachomatis, an obligately intracellular bacterium, is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. Numbers of U.S. infections of the urogenital tract and rectum have increased annually. Because C. trachomatis is not easily cultured, comparative genomic studies are limited, restricting our understanding of strain diversity and emergence among populations globally. While Agilent SureSelect(XT) target enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal samples, public access to these libraries is not available. We therefore designed an RNA bait library (34,795 120-mer probes based on 85 genomes, versus 33,619 probes using 74 genomes in a previous one) to augment organism sequencing from clinical samples that can be shared with the scientific community, enabling comparison studies. We describe the library and limit of detection for genome copy input, and we present results of 100% efficiency and high-resolution determination of recombination and identical genomes within vaginal-rectal specimen pairs in women. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, which limits our understanding of urogenital and rectal C. trachomatis transmission and impact on morbidity. To provide a publicly available workflow for whole-genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we developed and report on an RNA bait library to enrich the organism from clinical samples for sequencing. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis and identified recombinant and identical C. trachomatis genomes in paired vaginal-rectal samples from women. Our workflow provides a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital, and rectal infections and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity. |
Reply: Evidence of Recent Genomic Evolution in Gonococcal Strains With Decreased Susceptibility to Cephalosporins or Azithromycin in the United States, 2014-2016
Thomas JC , Kersh EN , Gernert KM , Shafer WM , Raphael BH . J Infect Dis 2020 221 (5) 852-853 We would like to extend our gratitude to Drs. Deng and Klausner for their interest in our article, in which we phylogenetically characterized gonococcal isolates collected through national sentinel surveillance and circulating in the United States, between 2014 and 2016 [1]. We identified 2 major subpopulations of strains associated with reduced susceptibility to either azithromycin (multilocus sequence typing [MLST] ST9363) or cephalosporins (MLST ST1901), and we detailed the evolution of several strains that possessed mutations that were not observed in the United States in 2000–2013. | | Antimicrobial resistance (AMR) in the gonococcus represents a major public health threat, chiefly due to its rapidly evolving nature and the increasingly limited number of available treatment options. Although routine surveillance of AMR in circulating strains is essential in monitoring this threat, an equally important practice involves the promotion of antibiotic stewardship in limiting the spread of resistance. It is notable that the Centers for Disease Control and Prevention’s Gonococcal Isolate Surveillance Project, a historic sentinel surveillance program, has tracked AMR trends for over 30 years and, more recently, included whole-genome sequencing (WGS) of a subset of isolates [2]. As a result, the implementation of WGS has generated massive quantities of genomic data that can be used in tandem with data from traditional antimicrobial susceptibility testing to examine AMR trends. In addition, the release of these data to the public repositories has facilitated the ability of other investigators to conduct a myriad of follow-up studies. |
Notes from the field: First case in the United States of Neisseria gonorrhoeae harboring emerging mosaic penA60 allele, conferring reduced susceptibility to cefixime and ceftriaxone
Picker MA , Knoblock RJ , Hansen H , Bautista I , Griego R , Barber L , Bendik W , Lam K , Adelman E , Qiu-Shultz Z , Raphael BH , Pham CD , Kersh EN , Weinstock H , St Cyr SB . MMWR Morb Mortal Wkly Rep 2020 69 (49) 1876-1877 In November 2019, the Southern Nevada Public Health Laboratory of the Southern Nevada Health District (SNHD) identified a male urethral gonococcal isolate later demonstrating reduced susceptibility to cefixime (minimum inhibitory concentration [MIC] = 2.0 μg/mL) and ceftriaxone (MIC = 1.0 μg/mL) but susceptible to azithromycin (MIC = 0.25 μg/mL). Molecular testing by CDC in the United States revealed the emerging mosaic penA60 allele, first identified in Japan in 2016 (1), which confers reduced susceptibility to cephalosporins and increases the risk for treatment failure. The penA60 allele has been identified in China (2), Canada (3,4), Denmark (5), Australia (6), France (7), and the United Kingdom (8). The Nevada case is the first identified case of a Neisseria gonorrhoeae isolate harboring the mosaic penA60 allele reported in the United States. |
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