Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Mathis S[original query] |
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Measles - United States, January 1, 2020-March 28, 2024
Mathis AD , Raines K , Masters NB , Filardo TD , Kim G , Crooke SN , Bankamp B , Rota PA , Sugerman DE . MMWR Morb Mortal Wkly Rep 2024 73 (14) 295-300 Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S. measles elimination status was threatened in 2019 as the result of two prolonged outbreaks among undervaccinated communities in New York and New York City. To assess U.S. measles elimination status after the 2019 outbreaks and to provide context to understand more recent increases in measles cases, CDC analyzed epidemiologic and laboratory surveillance data and the performance of the U.S. measles surveillance system after these outbreaks. During January 1, 2020-March 28, 2024, CDC was notified of 338 confirmed measles cases; 97 (29%) of these cases occurred during the first quarter of 2024, representing a more than seventeenfold increase over the mean number of cases reported during the first quarter of 2020-2023. Among the 338 reported cases, the median patient age was 3 years (range = 0-64 years); 309 (91%) patients were unvaccinated or had unknown vaccination status, and 336 case investigations included information on ≥80% of critical surveillance indicators. During 2020-2023, the longest transmission chain lasted 63 days. As of the end of 2023, because of the absence of sustained measles virus transmission for 12 consecutive months in the presence of a well-performing surveillance system, U.S. measles elimination status was maintained. Risk for widespread U.S. measles transmission remains low because of high population immunity. However, because of the increase in cases during the first quarter of 2024, additional activities are needed to increase U.S. routine measles, mumps, and rubella vaccination coverage, especially among close-knit and undervaccinated communities. These activities include encouraging vaccination before international travel and rapidly investigating suspected measles cases. |
Implications of measles inclusion by commercial syndromic polymerase chain reaction panels - United States, May 2022-April 2023
Thomas CM , Hartley A , Schmitz A , Reid HD , Sullivan S , Huebner E , Robinson M , Mathis A , Fill MA , Levinson KJ , Jones TF , Schaffner W , Newhouse CN , Dunn JR . MMWR Morb Mortal Wkly Rep 2024 73 (12) 260-264 Syndromic polymerase chain reaction (PCR) panels are used to test for pathogens that can cause rash illnesses, including measles. Rash illnesses have infectious and noninfectious causes, and approximately 5% of persons experience a rash 7-10 days after receipt of a measles, mumps, and rubella (MMR) vaccine. MMR vaccine includes live attenuated measles virus, which is detectable by PCR tests. No evidence exists of person-to-person transmission of measles vaccine virus, and illness does not typically result among immunocompetent persons. During September 2022-January 2023, the Tennessee Department of Health received two reports of measles detected by syndromic PCR panels. Both reports involved children (aged 1 and 6 years) without known risk factors for measles, who were evaluated for rash that occurred 11-13 days after routine MMR vaccination. After public health responses in Tennessee determined that both PCR panels had detected measles vaccine virus, six state health departments collaborated to assess the frequency and characteristics of persons receiving a positive measles PCR panel test result in the United States. Information was retrospectively collected from a commercial laboratory testing for measles in syndromic multiplex PCR panels. During May 2022-April 2023, among 1,548 syndromic PCR panels, 17 (1.1%) returned positive test results for measles virus. Among 14 persons who received a positive test result and for whom vaccination and case investigation information were available, all had received MMR vaccine a median of 12 days before specimen collection, and none had known risk factors for acquiring measles. All positive PCR results were attributed to detection of measles vaccine virus. Increased awareness among health care providers about potential measles detection by PCR after vaccination is needed. Any detection of measles virus by syndromic PCR testing should be immediately reported to public health agencies, which can use measles vaccination history and assessment of risk factors to determine the appropriate public health response. If a person recently received MMR vaccine and has no risk factors for acquiring measles, additional public health response is likely unnecessary. |
A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region
Unoarumhi Y , Davis ML , Rowe LA , Mathis S , Li Z , Chochua S , Li Y , McGee L , Metcalf BJ , Lee JS , Beall B . Sci Rep 2023 13 (1) 21510 Group A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0-43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain. |
Expansion of invasive group A streptococcus M1(uk) lineage in active bacterial core surveillance, United States, 2019‒2021
Li Y , Rivers J , Mathis S , Li Z , Chochua S , Metcalf BJ , Beall B , Onukwube J , Gregory CJ , McGee L . Emerg Infect Dis 2023 29 (10) 2116-2120 From 2015-2018 to 2019‒2021, hypertoxigenic M1(UK) lineage among invasive group A Streptococcus increased in the United States (1.7%, 21/1,230 to 11%, 65/603; p<0.001). M1(UK) was observed in 9 of 10 states, concentrated in Georgia (n = 41), Tennessee (n = 13), and New York (n = 13). Genomic cluster analysis indicated recent expansions. |
Notes from the field: Measles outbreak - central Ohio, 2022-2023
Tiller EC , Masters NB , Raines KL , Mathis AD , Crooke SN , Zwickl RC , French GK , Alexy ER , Koch EM , Tucker NE , Wilson EM , Krauss TS , Leasure E , Budd J , Billing LM , Dewart C , Tarter K , Dickerson K , Iyer R , Jones AN , Halabi KC , Washam MC , Sugerman DE , Roberts MW . MMWR Morb Mortal Wkly Rep 2023 72 (31) 847-849 On November 5, 2022, Columbus Public Health, Ohio and the Ohio Department of Health were notified of two children aged 2 years who were admitted to a central Ohio hospital with rash, fever, cough, and congestion, suggestive of measles. Both children were undergoing medical evaluation and treatment for other etiologies before measles was considered in the differential diagnosis. Neither child had received measles, mumps, and rubella (MMR) vaccine, and neither had known contact with a person with measles. Each patient subsequently received a positive measles real-time reverse transcription–polymerase chain reaction (RT-PCR) test result. Neither child had traveled internationally, but during June 12–October 8, 2022, four internationally imported measles cases had been confirmed among unvaccinated Franklin County, Ohio residents who had traveled to areas in East Africa where measles outbreaks were ongoing (1). Investigation of the U.S.-acquired measles cases identified additional measles cases, and local and state health departments confirmed a community outbreak on November 9, 2022. During this community measles outbreak in central Ohio, 85 locally acquired measles cases were confirmed with rash onsets during October 22–December 24, 2022; however, no definitive link to the previous international importations was established. The outbreak was declared over on February 4, 2023, 42 days (two measles incubation periods) after the last reported case. |
Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study
Masters NB , Beck AS , Mathis AD , Leung J , Raines K , Paul P , Stanley SE , Weg AL , Pieracci EG , Gearhart S , Jumabaeva M , Bankamp B , Rota PA , Sugerman DE , Gastañaduy PA . Lancet Public Health 2023 8 (8) e618-e628 BACKGROUND: On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures. METHODS: We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions. FINDINGS: 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission. INTERPRETATION: Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting. FUNDING: US Centers for Disease Control and Prevention. |
Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction.
Holcomb KM , Mathis S , Staples JE , Fischer M , Barker CM , Beard CB , Nett RJ , Keyel AC , Marcantonio M , Childs ML , Gorris ME , Rochlin I , Hamins-Puértolas M , Ray EL , Uelmen JA , DeFelice N , Freedman AS , Hollingsworth BD , Das P , Osthus D , Humphreys JM , Nova N , Mordecai EA , Cohnstaedt LW , Kirk D , Kramer LD , Harris MJ , Kain MP , Reed EMX , Johansson MA . Parasit Vectors 2023 16 (1) 11 BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases). |
Fecal shedding of two novel live attenuated oral poliovirus type 2 vaccines candidates by healthy bOPV/IPV-vaccinated infants: two randomized clinical trials.
Gast C , Bandyopadhyay AS , Sáez-Llorens X , De Leon T , DeAntonio R , Jimeno J , Aguirre G , McDuffie LM , Coffee E , Mathis DL , Oberste MS , Weldon WC , Konopka-Anstadt JL , Modlin J , Bachtiar NS , Fix A , Konz J , Clemens R , Costa Clemens SA , Rüttimann R . J Infect Dis 2022 226 (5) 852-861 BACKGROUND: Primary intestinal immunity through viral replication of live oral vaccine is key to interrupt poliovirus transmission. We assessed viral fecal shedding from infants administered Sabin monovalent poliovirus type 2 vaccine (mOPV2) or low and high doses of 2 novel OPV2 (nOPV2) vaccine candidates. METHODS: In 2 randomized clinical trials in Panama, a control mOPV2 study (October 2015 to April 2016) and nOPV2 study (September 2018 to October 2019), 18-week-old infants vaccinated with bivalent oral poliovirus vaccine/inactivated poliovirus vaccine received 1 or 2 study vaccinations 28 days apart. Stools were assessed for poliovirus RNA by polymerase chain reaction (PCR) and live virus by culture for 28 days postvaccination. RESULTS: Shedding data were available from 621 initially reverse-transcription PCR-negative infants (91 mOPV2, 265 nOPV2-c1, 265 nOPV2-c2 recipients). Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%-48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates 7 days after dose 2 decreased to 33.3% and 12.9%-22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2. CONCLUSIONS: Viral shedding of either nOPV candidate was similar or decreased relative to mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity. |
Invasive Group A Streptococcal Penicillin Binding Protein 2× Variants Associated with Reduced Susceptibility to β-Lactam Antibiotics in the United States, 2015-2021.
Chochua S , Metcalf B , Li Z , Mathis S , Tran T , Rivers J , Fleming-Dutra KE , Li Y , McGee L , Beall B . Antimicrob Agents Chemother 2022 66 (9) e0080222 All known group A streptococci [GAS] are susceptible to β-lactam antibiotics. We recently identified an invasive GAS (iGAS) variant (emm43.4/PBP2x-T553K) with unusually high minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin, although clinically susceptible to β-lactams. We aimed to quantitate PBP2x variants, small changes in β-lactam MICs, and lineages within contemporary population-based iGAS. PBP2x substitutions were comprehensively identified among 13,727 iGAS recovered during 2015-2021, in the USA. Isolates were subjected to antimicrobial susceptibility testing employing low range agar diffusion and PBP2x variants were subjected to phylogenetic analyses. Fifty-five variants were defined based upon substitutions within an assigned PBP2x transpeptidase domain. Twenty-nine of these variants, representing 338/13,727 (2.5%) isolates and 16 emm types, exhibited slightly elevated β-lactam MICs, none of which were above clinical breakpoints. The emm43.4/PBP2x-T553K variant, comprised of two isolates, displayed the most significant phenotype (ampicillin MIC 0.25 μg/ml) and harbored missense mutations within 3 non-PBP genes with known involvement in antibiotic efflux, membrane insertion of PBP2x, and peptidoglycan remodeling. The proportion of all PBP2x variants with elevated MICs remained stable throughout 2015-2021 (<3.0%). The predominant lineage (emm4/PBP2x-M593T/ermT) was resistant to macrolides/lincosamides and comprised 129/340 (37.9%) of isolates with elevated β-lactam MICs. Continuing β-lactam selective pressure is likely to have selected PBP2x variants that had escaped scrutiny due to MICs that remain below clinical cutoffs. Higher MICs exhibited by emm43.4/PBP2x-T553K are probably rare due to the requirement of additional mutations. Although elevated β-lactam MICs remain uncommon, emm43.4/PBP2x-T553K and emm4/PBP2x-M593T/ermT lineages indicate that antibiotic stewardship and strain monitoring is necessary. |
Evaluation of a wearable consumer noise measurement device in a laboratory setting
Roberts B , Jacobs N , Mathis C , Reamer H , Kardous C , Gaffney S , LNeitzel R . J Acoust Soc Am 2022 152 (1) 547-552 Exposure to noise occurs throughout daily life and, depending on the intensity, duration, and context, can lead to hearing loss, disturbed sleep, decreased academic achievement, and other negative health outcomes. Recently, smartwatches that use the device's onboard microphone to measure noise levels were released. This study evaluated the accuracy of these smartwatches in a controlled laboratory setting. For broadband pink noise, a total of 11 441 measurements were collected. The results showed that, on average, the smartwatch reported 3.4 dBA lower than the reference system on average. For the octave-band, a total of 18 449 measurements were collected. The smartwatch measured lower than the reference microphone from the 125 Hz to 1000 Hz octave bands, were somewhat in agreement at 2000 Hz, measured higher sound pressure levels than the reference microphone at 4000 Hz, and then lower at 8000 Hz. Despite not meeting the ANSI criteria for sound level meters, in some cases, these smartwatches still provide a reasonable degree of accuracy and have the potential for use in studies that require the measurement of personal noise exposure over an extended period. © 2022 Acoustical Society of America. |
Continued Increase of Erythromycin- and Clindamycin-Nonsusceptibility among Invasive Group A Streptococci Driven by Genomic Clusters, USA, 2018-2019.
Li Y , Rivers J , Mathis S , Li Z , McGee L , Chochua S , Metcalf BJ , Fleming-Dutra KE , Nanduri SA , Beall B . Clin Infect Dis 2022 76 (3) e1266-e1269 We analyzed 9630 invasive Group A Streptococci (iGAS) surveillance isolates in the USA. From 2015-2017 to 2018-2019, significant increases in erythromycin-nonsusceptibility (18% vs. 25%) and clindamycin-nonsusceptibility (17% vs. 24%) occurred, driven mainly by rapid expansions of genomic subclones. Prevention and control of clustered infections appear key to containing antimicrobial resistance. |
Public health actions to control measles among Afghan evacuees during Operation Allies Welcome - United States, September-November 2021
Masters NB , Mathis AD , Leung J , Raines K , Clemmons NS , Miele K , Balajee SA , Lanzieri TM , Marin M , Christensen DL , Clarke KR , Cruz MA , Gallagher K , Gearhart S , Gertz AM , Grady-Erickson O , Habrun CA , Kim G , Kinzer MH , Miko S , Oberste MS , Petras JK , Pieracci EG , Pray IW , Rosenblum HG , Ross JM , Rothney EE , Segaloff HE , Shepersky LV , Skrobarcek KA , Stadelman AM , Sumner KM , Waltenburg MA , Weinberg M , Worrell MC , Bessette NE , Peake LR , Vogt MP , Robinson M , Westergaard RP , Griesser RH , Icenogle JP , Crooke SN , Bankamp B , Stanley SE , Friedrichs PA , Fletcher LD , Zapata IA , Wolfe HO , Gandhi PH , Charles JY , Brown CM , Cetron MS , Pesik N , Knight NW , Alvarado-Ramy F , Bell M , Talley LE , Rotz LD , Rota PA , Sugerman DE , Gastañaduy PA . MMWR Morb Mortal Wkly Rep 2022 71 (17) 592-596 On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,(†) with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.(§) On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2). |
Genomic Insights on Variation Underlying Capsule Expression in Meningococcal Carriage Isolates From University Students, United States, 2015-2016.
Whaley MJ , Vuong JT , Topaz N , Chang HY , Thomas JD , Jenkins LT , Hu F , Schmink S , Steward-Clark E , Mathis M , Rodriguez-Rivera LD , Retchless AC , Joseph SJ , Chen A , Acosta AM , McNamara L , Soeters HM , Mbaeyi S , Marjuki H , Wang X . Front Microbiol 2022 13 815044 In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen. |
Maintenance of measles elimination status in the United States for 20 years despite increasing challenges
Mathis AD , Clemmons NS , Redd SB , Pham H , Leung J , Wharton AK , Anderson R , McNall RJ , Rausch-Phung E , Rosen JB , Blog D , Zucker JR , Bankamp B , Rota PA , Patel M , Gastañaduy PA . Clin Infect Dis 2021 75 (3) 416-424 BACKGROUND: Measles elimination (interruption of endemic measles virus transmission) in the United States was declared in 2000; however, the number of cases and outbreaks have increased in recent years. We characterized the epidemiology of measles outbreaks and measles transmission patterns post-elimination to identify potential gaps in the U.S. measles control program. METHODS: We analyzed national measles notification data from January 1, 2001-December 31, 2019. We defined measles infection clusters as single cases (isolated cases not linked to additional cases), 2-case clusters, or outbreaks with 3 or more linked cases. We calculated the effective reproduction number (R) to assess changes in transmissibility and reviewed molecular epidemiology data. RESULTS: During 2001-2019, 3,873 measles cases, including 747 international importations, were reported in the United States; 29% of importations were associated with outbreaks. Among 871 clusters, 69% were single cases and 72% had no spread. Larger and longer clusters were reported since 2013, including seven outbreaks with >50 cases lasting >2 months, 5 of which occurred in known underimmunized, close-knit communities. No measles lineage circulated in a single transmission chain for >12 months. Higher estimates of R were noted in recent years, although R remained below the epidemic threshold of 1. CONCLUSIONS: Current epidemiology continues to support the interruption of endemic measles virus transmission in the United States. However, larger and longer outbreaks in recent post-elimination years and emerging trends of increased transmission in underimmunized communities emphasize the need for targeted approaches to close existing immunity gaps and maintain measles elimination. |
Genomic Characterization of Group A Streptococci Causing Pharyngitis and Invasive Disease in Colorado, USA, June 2016 - April 2017.
Li Y , Dominguez S , Nanduri SA , Rivers J , Mathis S , Li Z , McGee L , Chochua S , Metcalf BJ , Van Beneden CA , Beall B , Miller L . J Infect Dis 2021 225 (10) 1841-1851 BACKGROUND: The genomic features and transmission link of circulating Group A streptococcus (GAS) strains causing different disease types, such as pharyngitis and invasive disease, are not well understood. METHODS: We used whole-genome sequencing (WGS) to characterize GAS isolates recovered from persons with pharyngitis and invasive disease in the Denver metropolitan area from June 2016 to April 2017. RESULTS: GAS isolates were cultured from 236 invasive and 417 pharyngitis infections. WGS identified 34 emm types. Compared to pharyngitis isolates, invasive isolates were more likely to carry the erm family genes (23% vs. 7.4%, p<0.001), which confer resistance to erythromycin and clindamycin (including inducible resistance), and covS gene inactivation (7% vs. 0.5%, p<0.001). WGS identified 97 genomic clusters (433 isolates; 2-65 isolates per cluster) that consisted of genomically closely related isolates (median SNP (IQR) = 3 (1-4) within cluster). Thirty genomic clusters (200 isolates; 31% of all isolates) contained both pharyngitis and invasive isolates and were found in 11 emm types. CONCLUSIONS: In the Denver metropolitan population, mixed disease types were commonly seen in clusters of closely related isolates, indicative of overlapping transmission networks. Antibiotic-resistance and covS inactivation was disproportionally associated with invasive disease. |
West Nile virus and other domestic nationally notifiable arboviral diseases - United States, 2019
Vahey GM , Mathis S , Martin SW , Gould CV , Staples JE , Lindsey NP . MMWR Morb Mortal Wkly Rep 2021 70 (32) 1069-1074 Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses, including La Crosse, Jamestown Canyon, Powassan, eastern equine encephalitis, and St. Louis encephalitis viruses, cause sporadic disease and occasional outbreaks. This report summarizes surveillance data for nationally notifiable domestic arboviruses reported to CDC for 2019. For 2019, 47 states and the District of Columbia (DC) reported 1,173 cases of domestic arboviral disease, including 971 (83%) WNV disease cases. Among the WNV disease cases, 633 (65%) were classified as neuroinvasive disease, for a national incidence of 0.19 cases per 100,000 population, 53% lower than the median annual incidence during 2009-2018. More Powassan and eastern equine encephalitis virus disease cases were reported in 2019 than in any previous year. Health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis, perform recommended diagnostic testing, and promptly report cases to public health authorities. Because arboviral diseases continue to cause serious illness, and annual incidence of individual viruses continues to vary with sporadic outbreaks, maintaining surveillance is important in directing prevention activities. Prevention depends on community and household efforts to reduce vector populations and personal protective measures to prevent mosquito and tick bites such as use of Environmental Protection Agency-registered insect repellent and wearing protective clothing.*(,)(†). |
Surveillance for West Nile Virus Disease - United States, 2009-2018
McDonald E , Mathis S , Martin SW , Staples JE , Fischer M , Lindsey NP . MMWR Surveill Summ 2021 70 (1) 1-15 PROBLEM/CONDITION: West Nile virus (WNV) is an arthropodborne virus (arbovirus) in the family Flaviviridae and is the leading cause of domestically acquired arboviral disease in the contiguous United States. An estimated 70%-80% of WNV infections are asymptomatic. Symptomatic persons usually develop an acute systemic febrile illness. Less than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. REPORTING PERIOD: 2009-2018. DESCRIPTION OF SYSTEM: WNV disease is a nationally notifiable condition with standard surveillance case definitions. State health departments report WNV cases to CDC through ArboNET, an electronic passive surveillance system. Variables collected include patient age, sex, race, ethnicity, county and state of residence, date of illness onset, clinical syndrome, hospitalization, and death. RESULTS: During 2009-2018, a total of 21,869 confirmed or probable cases of WNV disease, including 12,835 (59%) WNV neuroinvasive disease cases, were reported to CDC from all 50 states, the District of Columbia, and Puerto Rico. A total of 89% of all WNV patients had illness onset during July-September. Neuroinvasive disease incidence and case-fatalities increased with increasing age, with the highest incidence (1.22 cases per 100,000 population) occurring among persons aged ≥70 years. Among neuroinvasive cases, hospitalization rates were >85% in all age groups but were highest among patients aged ≥70 years (98%). The national incidence of WNV neuroinvasive disease peaked in 2012 (0.92 cases per 100,000 population). Although national incidence was relatively stable during 2013-2018 (average annual incidence: 0.44; range: 0.40-0.51), state level incidence varied from year to year. During 2009-2018, the highest average annual incidence of neuroinvasive disease occurred in North Dakota (3.16 cases per 100,000 population), South Dakota (3.06), Nebraska (1.95), and Mississippi (1.17), and the largest number of total cases occurred in California (2,819), Texas (2,043), Illinois (728), and Arizona (632). Six counties located within the four states with the highest case counts accounted for 23% of all neuroinvasive disease cases nationally. INTERPRETATION: Despite the recent stability in annual national incidence of neuroinvasive disease, peaks in activity were reported in different years for different regions of the country. Variations in vectors, avian amplifying hosts, human activity, and environmental factors make it difficult to predict future WNV disease incidence and outbreak locations. PUBLIC HEALTH ACTION: WNV disease surveillance is important for detecting and monitoring seasonal epidemics and for identifying persons at increased risk for severe disease. Surveillance data can be used to inform prevention and control activities. Health care providers should consider WNV infection in the differential diagnosis of aseptic meningitis and encephalitis, obtain appropriate specimens for testing, and promptly report cases to public health authorities. Public health education programs should focus prevention messaging on older persons, because they are at increased risk for severe neurologic disease and death. In the absence of a human vaccine, WNV disease prevention depends on community-level mosquito control and household and personal protective measures. Understanding the geographic distribution of cases, particularly at the county level, appears to provide the best opportunity for directing finite resources toward effective prevention and control activities. Additional work to further develop and improve predictive models that can foreshadow areas most likely to be impacted in a given year by WNV outbreaks could allow for proactive targeting of interventions and ultimately lowering of WNV disease morbidity and mortality. |
COVID-19 Investigational Treatments in Use Among Hospitalized Patients Identified Through the US Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, March 1-June 30, 2020.
Acosta AM , Mathis AL , Budnitz DS , Geller AI , Chai SJ , Alden NB , Meek J , Anderson EJ , Ryan P , Kim S , Como-Sabetti K , Torres S , Dufort E , Bennett NM , Billing LM , Sutton M , Keipp Talbot H , George A , Pham H , Hall AJ , Fry A , Garg S , Kim L . Open Forum Infect Dis 2020 7 (11) ofaa528 Using a coronavirus disease 2019 (COVID-19)-associated hospitalization surveillance network, we found that 42.5% of hospitalized COVID-19 cases with available data from March 1-June 30, 2020, received ≥1 COVID-19 investigational treatment. Hydroxychloroquine, azithromycin, and remdesivir were used frequently; however, hydroxychloroquine and azithromycin use declined over time, while use of remdesivir increased. |
Genomic Surveillance of Streptococcus pyogenes Strains Causing Invasive Disease, United States, 2016-2017.
Li Y , Rivers J , Mathis S , Li Z , Velusamy S , Nanduri SA , Van Beneden CA , Snippes-Vagnone P , Lynfield R , McGee L , Chochua S , Metcalf BJ , Beall B . Front Microbiol 2020 11 1547 Background: Streptococcus pyogenes is a major cause of severe, invasive infections in humans. The bacterial pathogen harbors a wide array of virulence factors and exhibits high genomic diversity. Rapid changes of circulating strains in a community are common. Understanding the current prevalence and dynamics of S. pyogenes lineages could inform vaccine development and disease control strategies. Methods: We used whole-genome sequencing (WGS) to characterize all invasive S. pyogenes isolates obtained through the United States Center for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) in 2016 and 2017. We determined the distribution of strain features, including emm type, antibiotic resistance determinants, and selected virulence factors. Changes in strain feature distribution between years 2016 and 2017 were evaluated. Phylogenetic analysis was used to identify expanding lineages within emm type. Results: Seventy-one emm types were identified from 3873 isolates characterized. The emm types targeted by a 30-valent M protein-based vaccine accounted for 3230 (89%) isolates. The relative frequencies of emm types collected during the 2 years were similar. While all isolates were penicillin-susceptible, erythromycin-resistant isolates increased from 273 (16% of 2016 isolates) to 432 (23% of 2017 isolates), mainly driven by increase of the erm-positive emm types 92 and 83. The prevalence of 24 virulence factors, including 11 streptococcal pyrogenic toxins, ranged from 6 to 90%. In each of three emm types (emm 49, 82, and 92), a subgroup of isolates significantly expanded between 2016 and 2017 compared to isolates outside of the subgroup (P-values < 0.0001). Specific genomic sequence changes were associated with these expanded lineages. Conclusions: While the overall population structure of invasive S. pyogenes isolates in the United States remained stable, some lineages, including several that were antibiotic-resistant, increased between 2016 and 2017. Continued genomic surveillance can help monitor and characterize bacterial features associated with emerging strains from invasive infections. |
Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive Group B Streptococci within the US: 2015-2017.
McGee L , Chochua S , Li Z , Mathis S , Rivers J , Metcalf B , Ryan A , Alden N , Farley MM , Harrison LH , Snippes Vagnone P , Lynfield R , Smelser C , Muse A , Thomas AR , Schrag S , Beall BW . Clin Infect Dis 2020 72 (6) 1004-1013 BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS: Using whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states. RESULTS: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more beta-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2microg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS: This first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring. |
Pathogen surveillance in the informal settlement, Kibera, Kenya, using a metagenomics approach.
Hendriksen RS , Lukjancenko O , Munk P , Hjelmso MH , Verani JR , Ng'eno E , Bigogo G , Kiplangat S , Oumar T , Bergmark L , Roder T , Neatherlin JC , Clayton O , Hald T , Karlsmose S , Pamp SJ , Fields B , Montgomery JM , Aarestrup FM . PLoS One 2019 14 (10) e0222531 BACKGROUND: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate. METHOD: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance. RESULTS: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time. CONCLUSION: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care. |
Emergent Invasive Group A Streptococcus dysgalactiae subsp. Equisimilis, United States, 2015-2018.
Chochua S , Rivers J , Mathis S , Li Z , Velusamy S , McGee L , Van Beneden C , Li Y , Metcalf BJ , Beall B . Emerg Infect Dis 2019 25 (8) 1543-1547 The term group A Streptococcus is considered synonymous for the species Streptococcus pyogenes. We describe an emergent invasive S. dysgalactiae subspecies equisimilis lineage that obtained the group A antigen through a single ancestral recombination event between a group C S. dysgalactiae subsp. equisimilis strain and a group A S. pyogenes strain. |
Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012-2015
Alvarado LI , Lorenzi OD , Torres-Velasquez BC , Sharp TM , Vargas L , Munoz-Jordan JL , Hunsperger EA , Perez-Padilla J , Rivera A , Gonzalez-Zeno GE , Galloway RL , Glass Elrod M , Mathis DL , Oberste MS , Nix WA , Henderson E , McQuiston J , Singleton J , Kato C , Garcia-Gubern C , Santiago-Rivera W , Muns-Sosa R , Ortiz-Rivera JD , Jimenez G , Rivera-Amill V , Andujar-Perez DA , Horiuchi K , Tomashek KM . PLoS Negl Trop Dis 2019 13 (7) e0007562 Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever </=7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI. |
Association between third-trimester Tdap immunization and neonatal pertussis antibody concentration
Healy CM , Rench MA , Swaim LS , Smith EO , Sangi-Haghpeykar H , Mathis MH , Martin MD , Baker CJ . JAMA 2018 320 (14) 1464-1470 Importance: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. Objective: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. Design, Setting, and Participants: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). Exposures: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. Main Outcomes and Measures: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. Results: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% [95% CI, 42%-55%]), 30 IU/mL or higher (72% vs 17%; difference, 55% [95% CI, 49%-61%]), and 40 IU/mL or higher (59% vs 12%; difference, 47% [95% CI, 41%-54%]); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL [95% CI, 44.0-74.6]). Conclusions and Relevance: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations. |
Screening and genomic characterization of filamentous hemagglutinin-deficient Bordetella pertussis.
Weigand MR , Pawloski LC , Peng Y , Ju H , Burroughs M , Cassiday PK , Davis JK , DuVall M , Johnson T , Juieng P , Knipe K , Loparev VN , Mathis MH , Rowe LA , Sheth M , Williams MM , Tondella ML . Infect Immun 2018 86 (4) Despite high vaccine coverage, pertussis cases in the United States (US) have increased over the last decade. Growing evidence suggests that disease resurgence results, in part, from genetic divergence of circulating strain populations away from vaccine references. The US exclusively employs acellular vaccines and current Bordetella pertussis isolates are predominantly deficient in at least one immunogen, pertactin (Prn). First detected in the US retrospectively in a 1994 isolate, the rapid spread of Prn deficiency is likely vaccine driven, raising concerns about whether other acellular vaccine immunogens experience similar pressures as further antigenic changes could potentially threaten vaccine efficacy. We developed an electrochemiluminescent antibody capture assay to monitor production of the acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 US surveillance isolates collected from 2010-2016 identified two that were both Prn- and Fha-deficient. Three additional Fha-deficient laboratory strains were also identified from a historic collection of 65 isolates dating back to 1935. Whole-genome sequencing of deficient isolates revealed putative, underlying genetic changes. Only four isolates harbored mutation to known genes involved in Fha production, highlighting the complexity of its regulation. The chromosomes of two Fha-deficient isolates included unexpected structural variation that did not appear to influence Fha production. Furthermore, insertion sequence disruption of fhaB was also detected in a previously identified pertussis toxin-deficient isolate that still produced normal levels of Fha. These results demonstrate the genetic potential for additional vaccine immunogen deficiency and underscore the importance of continued surveillance of circulating B. pertussis evolution in response to vaccine pressure. |
Population and Whole Genome Sequence Based Characterization of Invasive Group A Streptococci Recovered in the United States during 2015.
Chochua S , Metcalf BJ , Li Z , Rivers J , Mathis S , Jackson D , Gertz RE Jr , Srinivasan V , Lynfield R , Van Beneden C , McGee L , Beall B . mBio 2017 8 (5) Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3). Sixty-four M protein gene (emm) types were identified among 69 clonal complexes (CCs), including one CC of Streptococcus dysgalactiae subsp. equisimilisemm types predicted the presence or absence of active sof determinants and were segregated into sof-positive or sof-negative genetic complexes. Only one "emm type switch" between strains was apparent. sof-negative strains showed a propensity to cause infections in the first quarter of the year, while sof+ strain infections were more likely in summer. Of 1,454 isolates, 808 (55.6%) were Pnga3 positive and 637 (78.9%) were accounted for by types emm1, emm89, and emm12 Theoretical coverage of a 30-valent M vaccine combined with an M-related protein (Mrp) vaccine encompassed 98% of the isolates. WGS data predicted that 15.3, 13.8, 12.7, and 0.6% of the isolates were nonsusceptible to tetracycline, erythromycin plus clindamycin, erythromycin, and fluoroquinolones, respectively, with only 19 discordant phenotypic results. Close phylogenetic clustering of emm59 isolates was consistent with recent regional emergence. This study revealed strain traits informative for GAS disease incidence tracking, outbreak detection, vaccine strategy, and antimicrobial therapy.IMPORTANCE The current population-based WGS data from GAS strains causing invasive disease in the United States provide insights important for prevention and control strategies. Strain distribution data support recently proposed multivalent M type-specific and conserved M-like protein vaccine formulations that could potentially protect against nearly all invasive U.S. strains. The three most prevalent clonal complexes share key polymorphisms in the nga operon encoding two secreted virulence factors (NADase and streptolysin O) that have been previously associated with high strain virulence and transmissibility. We find that Streptococcus pyogenes is phylogenetically subdivided into loosely defined multilocus sequence type-based clusters consisting of solely sof-negative or sof-positive strains; with sof-negative strains demonstrating differential seasonal preference for infection, consistent with the recently demonstrated differential seasonal preference based on phylogenetic clustering of full-length M proteins. This might relate to the differences in GAS strain compositions found in different geographic settings and could further inform prevention strategies. |
Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015
Tomashek KM , Lorenzi OD , Andujar-Perez DA , Torres-Velasquez BC , Hunsperger EA , Munoz-Jordan JL , Perez-Padilla J , Rivera A , Gonzalez-Zeno GE , Sharp TM , Galloway RL , Glass Elrod M , Mathis DL , Oberste MS , Nix WA , Henderson E , McQuiston J , Singleton J , Kato C , Garcia Gubern C , Santiago-Rivera W , Cruz-Correa J , Muns-Sosa R , Ortiz-Rivera JD , Jimenez G , Galarza IE , Horiuchi K , Margolis HS , Alvarado LI . PLoS Negl Trop Dis 2017 11 (9) e0005859 Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management. |
Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the United States.
Metcalf BJ , Chochua S , Gertz RE Jr , Hawkins PA , Ricaldi J , Li Z , Walker H , Tran T , Rivers J , Mathis S , Jackson D , Glennen A , Lynfield R , McGee L , Beall B . Clin Microbiol Infect 2017 23 (8) 574 e7-574 e14 OBJECTIVES: Our objective was to evaluate and exploit a whole genome sequence (WGS) bioinformatics pipeline for predicting antimicrobial resistance and capsular serotypes from invasive group B streptococci (iGBS). METHODS: For 1975 iGBS recovered during 2015 from CDC's Active Bacterial Core surveillance, we compared pipeline predictions to broth dilution testing. Fifty-six isolates from earlier surveillance were included for testing beta-lactams.. Conventional serotyping was compared to WGS-based assignments for 302 isolates. RESULTS: All 28 isolates with reduced susceptibility to beta-lactam antibiotics harbored one of 19 rare PBP2x types. Resistances to erythromycin/clindamycin (808/1975 isolates, 41.0%), erythromycin (235/1975, 11.9%), and lincosamide/streptogramin A/pleuromutilins (56/1975, 2.8%) were predicted by presence of erm-methylase, mef, and lsa determinants, respectively (41 of 56 lsa gene positive isolates also contained lnu, erm, and/or mef genes). Presence of both erm and lsa determinants (25 isolates) predicted nonsusceptibility to quinupristin/dalfopristin. Most isolates (1680/1975, 85.1%) were tet gene-positive, although 41/1565 (2.6%) tetM-positive isolates were tetracycline-susceptible. All 53 fluoroquinolone-resistant isolates contained ParC and/or GyrA substitutions. Resistances to rifampin (8 isolates), trimethoprim, chloramphenicol and vancomycin (2 isolates each) were predicted by the pipeline. Resistance to macrolides/lincosamides without pipeline prediction was rare and correlated to divergent resistance genes or rRNA A2062G substitution. A selection of 267 isolates assigned WGS-based serotypes were also conventionally serotyped. Of these, 246 (92.1%) were in agreement, with the remaining 21 (7.8%) conventionally non-serotypeable. For thirty-two of 1975 isolates (1.6%), WGS-based serotypes could not be assigned. CONCLUSION: WGS-based assignment of iGBS resistance features and serotypes is an accurate substitute for phenotypic testing. |
The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement.
Weigand MR , Peng Y , Loparev V , Batra D , Bowden KE , Burroughs M , Cassiday PK , Davis JK , Johnson T , Juieng P , Knipe K , Mathis MH , Pruitt AM , Rowe L , Sheth M , Tondella ML , Williams MM . J Bacteriol 2017 199 (8) Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although Bordetella pertussis is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genome structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 B. pertussis isolates to examine potential evolution of chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. Observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with >240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in B. pertussis is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigation of disease resurgence and molecular epidemiology. IMPORTANCE: Whooping cough, primarily caused by Bordetella pertussis, has resurged in the United States even though coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of B. pertussis includes a high number of repetitive, mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-coding genes which otherwise exhibit little nucleotide sequence diversity. By comparing complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology. |
Brucella placentitis and seroprevalence in northern fur seals (Callorhinus ursinus) of the Pribilof Islands, Alaska
Duncan CG , Tiller R , Mathis D , Stoddard R , Kersh GJ , Dickerson B , Gelatt T . J Vet Diagn Invest 2014 26 (4) 507-512 Brucella species infect a wide range of hosts with a broad spectrum of clinical manifestations. In mammals, one of the most significant consequences of Brucella infection is reproductive failure. There is evidence of Brucella exposure in many species of marine mammals, but the outcome of infection is often challenging to determine. The eastern Pacific stock of northern fur seals (NFSs, Callorhinus ursinus) has declined significantly, spawning research into potential causes for this trend, including investigation into reproductive health. The objective of the current study was to determine if NFSs on St. Paul Island, Alaska have evidence of Brucella exposure or infection. Archived DNA extracted from placentas (n = 119) and serum (n = 40) samples were available for testing by insertion sequence (IS) 711 polymerase chain reaction (PCR) and the Brucella microagglutination test (BMAT), respectively. As well, placental tissue was available for histologic examination. Six (5%) placentas were positive by PCR, and a single animal had severe placentitis. Multilocus variable number tandem repeat analysis profiles were highly clustered and closely related to other Brucella pinnipedialis isolates. A single animal was positive on BMAT, and 12 animals had titers within the borderline range; 1 borderline animal was positive by PCR on serum. The findings suggest that NFSs on the Pribilof Islands are exposed to Brucella and that the organism has the ability to cause severe placental disease. Given the population trend of the NFS, and the zoonotic nature of this pathogen, further investigation into the epidemiology of this disease is recommended. |
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