Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Dalton A[original query] |
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Notes from the field: Long COVID prevalence among adults - United States, 2022
Ford ND , Agedew A , Dalton AF , Singleton J , Perrine CG , Saydah S . MMWR Morb Mortal Wkly Rep 2024 73 (6) 135-136 |
Long COVID and significant activity limitation among adults, by age - United States, June 1-13, 2022, to June 7-19, 2023
Ford ND , Slaughter D , Edwards D , Dalton A , Perrine C , Vahratian A , Saydah S . MMWR Morb Mortal Wkly Rep 2023 72 (32) 866-870 Long COVID is a condition encompassing a wide range of health problems that emerge, persist, or return following COVID-19. CDC analyzed national repeat cross-sectional Household Pulse Survey data to estimate the prevalence of long COVID and significant related activity limitation among U.S. adults aged ≥18 years by age group. Data from surveys completed between June 1-13, 2022, and June 7-19, 2023, indicated that long COVID prevalence decreased from 7.5% (95% CI = 7.1-7.9) to 6.0% (95% CI = 5.7-6.3) among the overall U.S. adult population, irrespective of history of previous COVID-19, and from 18.9% (95% CI = 17.9-19.8) to 11.0% (95% CI = 10.4-11.6) among U.S. adults reporting previous COVID-19. Among both groups, prevalence decreased from June 1-13, 2022, through January 4-16, 2023, before stabilizing. When stratified by age, only adults aged <60 years experienced significant rates of decline (p<0.01). Among adults reporting previous COVID-19, prevalence decreased among those aged 30-79 years through fall or winter and then stabilized. During June 7-19, 2023, 26.4% (95% CI = 24.0-28.9) of adults with long COVID reported significant activity limitation, the prevalence of which did not change over time. These findings help guide the ongoing COVID-19 prevention efforts and planning for long COVID symptom management and future health care service needs. |
Validation of novel Mycobacterium tuberculosis isoniazid resistance mutations not detectable by common molecular tests (preprint)
Kandler JL , Mercante AD , Dalton TL , Ezewudo MN , Cowan LS , Burns SP , Metchock B , Cegielski P , Posey JE . bioRxiv 2018 322750 Resistance to the first-line anti-tuberculosis (TB) drug, isoniazid (INH), is widespread, and the mechanism of resistance is unknown in approximately 15% of INH-resistant (INH-R) strains. To improve molecular detection of INH-R TB, we used whole genome sequencing (WGS) to analyze 52 phenotypically INH-R Mycobacterium tuberculosis complex (MTBC) clinical isolates that lacked the common katG S315T or inhA promoter mutations. Approximately 94% (49/52) of strains had mutations at known INH-associated loci that were likely to confer INH resistance. All such mutations would be detectable by sequencing more DNA adjacent to existing target regions. Use of WGS minimized the chances of missing infrequent INH resistance mutations outside commonly targeted hotspots. We used recombineering to generate 12 observed clinical katG mutations in the pansusceptible H37Rv reference strain and determined their impact on INH resistance. Our functional genetic experiments have confirmed the role of seven suspected INH resistance mutations and discovered five novel INH resistance mutations. All recombineered katG mutations conferred resistance to INH at a minimum inhibitory concentration of ≥0.25 μg/mL and should be added to the list of INH resistance determinants targeted by molecular diagnostic assays. We conclude that WGS is a superior method for detection of INH-R MTBC compared to current targeted molecular testing methods and could provide earlier diagnosis of drug-resistant TB. |
Number needed to vaccinate with a COVID-19 booster to prevent a COVID-19-associated hospitalization during SARS-CoV-2 Omicron BA.1 variant predominance, December 2021-February 2022, VISION Network: a retrospective cohort study
Adams K , Riddles JJ , Rowley EAK , Grannis SJ , Gaglani M , Fireman B , Hartmann E , Naleway AL , Stenehjem E , Hughes A , Dalton AF , Natarajan K , Dascomb K , Raiyani C , Irving SA , Sloan-Aagard C , Kharbanda AB , DeSilva MB , Dixon BE , Ong TC , Keller J , Dickerson M , Grisel N , Murthy K , Nanez J , Fadel WF , Ball SW , Patel P , Arndorfer J , Mamawala M , Valvi NR , Dunne MM , Griggs EP , Embi PJ , Thompson MG , Link-Gelles R , Tenforde MW . Lancet Reg Health Am 2023 23 100530 BACKGROUND: Understanding the usefulness of additional COVID-19 vaccine doses-particularly given varying disease incidence-is needed to support public health policy. We characterize the benefits of COVID-19 booster doses using number needed to vaccinate (NNV) to prevent one COVID-19-associated hospitalization or emergency department encounter. METHODS: We conducted a retrospective cohort study of immunocompetent adults at five health systems in four U.S. states during SARS-CoV-2 Omicron BA.1 predominance (December 2021-February 2022). Included patients completed a primary mRNA COVID-19 vaccine series and were either eligible to or received a booster dose. NNV were estimated using hazard ratios for each outcome (hospitalization and emergency department encounters), with results stratified by three 25-day periods and site. FINDINGS: 1,285,032 patients contributed 938 hospitalizations and 2076 emergency department encounters. 555,729 (43.2%) patients were aged 18-49 years, 363,299 (28.3%) 50-64 years, and 366,004 (28.5%) ≥65 years. Most patients were female (n = 765,728, 59.6%), White (n = 990,224, 77.1%), and non-Hispanic (n = 1,063,964, 82.8%). 37.2% of patients received a booster and 62.8% received only two doses. Median estimated NNV to prevent one hospitalization was 205 (range 44-615) and NNV was lower across study periods for adults aged ≥65 years (110, 46, and 88, respectively) and those with underlying medical conditions (163, 69, and 131, respectively). Median estimated NNV to prevent one emergency department encounter was 156 (range 75-592). INTERPRETATION: The number of patients needed to receive a booster dose was highly dependent on local disease incidence, outcome severity, and patient risk factors for moderate-to-severe disease. FUNDING: Funding was provided by the Centers for Disease Control and Prevention though contract 75D30120C07986 to Westat, Inc. and contract 75D30120C07765 to Kaiser Foundation Hospitals. |
Estimated effectiveness of JYNNEOS vaccine in preventing Mpox: A Multijurisdictional Case-Control Study - United States, August 19, 2022-March 31, 2023
Dalton AF , Diallo AO , Chard AN , Moulia DL , Deputy NP , Fothergill A , Kracalik I , Wegner CW , Markus TM , Pathela P , Still WL , Hawkins S , Mangla AT , Ravi N , Licherdell E , Britton A , Lynfield R , Sutton M , Hansen AP , Betancourt GS , Rowlands JV , Chai SJ , Fisher R , Danza P , Farley M , Zipprich J , Prahl G , Wendel KA , Niccolai L , Castilho JL , Payne DC , Cohn AC , Feldstein LR . MMWR Morb Mortal Wkly Rep 2023 72 (20) 553-558 As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,(†) including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,(§) to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),(¶) regardless of administration route or immunocompromise status. |
Vaccine effectiveness of JYNNEOS against mpox disease in the United States
Deputy NP , Deckert J , Chard AN , Sandberg N , Moulia DL , Barkley E , Dalton AF , Sweet C , Cohn AC , Little DR , Cohen AL , Sandmann D , Payne DC , Gerhart JL , Feldstein LR . N Engl J Med 2023 388 (26) 2434-2443 BACKGROUND: In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route. METHODS: We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100. RESULTS: Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1). CONCLUSIONS: In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.). |
Use of Nucleic Acid Amplification Testing for Rapid Detection of Mycobacterium tuberculosis Complex Among US Tuberculosis Patients, 2011‒2017.
Kumar V , Dalton TL , Armstrong LR , Whitesell A , Li R , Starks AM . Open Forum Infect Dis 2021 8 (11) ofab528 BACKGROUND: Nucleic acid amplification (NAA) tests rapidly detect Mycobacterium tuberculosis complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis. METHODS: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017. RESULTS: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.9%) were reported as not having an NAA test performed; the proportion without NAA testing declined annually, from 60.5% in 2011 to 33.6% in 2017. Of 67082 verified cases, 27912 (41.6%) had positive, 8215 (12.2%) had negative, and 135 (0.2%) had indeterminate NAA test results. Among the 33937 cases with an acid-fast bacilli (AFB) smear-positive result, 24093 (70.9%) had an NAA test performed; 11490 of the 30244 (38.0%) with an AFB smear-negative result had an NAA test performed. Although sputum was the most common specimen type tested, 79.8% (7023/8804) of nonsputum specimen types had a positive NAA test result. Overall, 63.7% of cases with laboratory testing had NAA test results reported <6 days following specimen collection; for 13891 cases not yet on treatment, median time to treatment after the laboratory report date was 2 days. CONCLUSIONS: Our analyses demonstrate increased NAA test utilization between 2011 and 2017. However, a large proportion of cases did not have an NAA test performed, reflecting challenges in broader uptake, suggesting an opportunity to expand use of this diagnostic methodology. |
Effectiveness of BNT162b2 COVID-19 Vaccination in Children and Adolescents.
Klein NP , Demarco M , Fleming-Dutra KE , Stockwell MS , Kharbanda AB , Gaglani M , Rao S , Lewis N , Irving SA , Hartmann E , Natarajan K , Dalton AF , Zerbo O , DeSilva MB , Konatham D , Stenehjem E , Rowley EAK , Ong TC , Grannis SJ , Sloan-Aagard C , Han J , Verani JR , Raiyani C , Dascomb K , Reese SE , Barron MA , Fadel WF , Naleway AL , Nanez J , Dickerson M , Goddard K , Murthy K , Grisel N , Weber ZA , Dixon BE , Patel P , Fireman B , Arndorfer J , Valvi NR , Griggs EP , Hallowell C , Embi PJ , Ball SW , Thompson MG , Tenforde MW , Link-Gelles R . Pediatrics 2023 151 (5) OBJECTIVES: We assessed BNT162b2 vaccine effectiveness (VE) against mild to moderate and severe coronavirus disease 2019 (COVID-19) in children and adolescents through the Omicron BA.4/BA.5 period. METHODS: Using VISION Network records from April 2021 to September 2022, we conducted a test-negative, case-control study assessing VE against COVID-19-associated emergency department/urgent care (ED/UC) encounters and hospitalizations using logistic regression, conditioned on month and site, adjusted for covariates. RESULTS: We compared 9800 ED/UC cases with 70 232 controls, and 305 hospitalized cases with 2612 controls. During Delta, 2-dose VE against ED/UC encounters at 12 to 15 years was initially 93% (95% confidence interval 89 to 95), waning to 77% (69% to 84%) after ≥150 days. At ages 16 to 17, VE was initially 93% (86% to 97%), waning to 72% (63% to 79%) after ≥150 days. During Omicron, VE at ages 12 to 15 was initially 64% (44% to 77%), waning to 13% (3% to 23%) after ≥150 days; at ages 16 to 17 VE was 31% (10% to 47%) during days 60 to 149, waning to 7% (-8 to 20%) after 150 days. A monovalent booster increased VE to 54% (40% to 65%) at ages 12 to 15 and 46% (30% to 58%) at ages 16 to 17. At ages 5 to 11, 2-dose VE was 49% (33% to 61%) initially and 41% (29% to 51%) after 150 days. During Delta, VE against hospitalizations at ages 12 to 17 was high (>97%), and at ages 16 to 17 remained 98% (73% to 100%) beyond 150 days; during Omicron, hospitalizations were too infrequent to precisely estimate VE. CONCLUSIONS: BNT162b2 protected children and adolescents against mild to moderate and severe COVID-19. VE was lower during Omicron predominance including BA.4/BA.5, waned after dose 2 but increased after a monovalent booster. Children and adolescents should receive all recommended COVID-19 vaccinations. |
Burkholderia pseudomallei laboratory exposure, Arizona, USA
Speiser LJ , Graf EH , Seville MT , Singbartl K , Dalton ML , Harrington D , Kretschmer M , Kuljanin M , Zabel K , Sunenshine R , Ruberto I , Venkat H , Grys TE . Emerg Infect Dis 2023 29 (5) 1061-1063 We describe an incidental Burkholderia pseudomallei laboratory exposure in Arizona, USA. Because melioidosis cases are increasing in the United States and B. pseudomallei reservoirs have been discovered in the Gulf Coast Region, US laboratory staff could be at increased risk for B. pseudomallei exposure. |
Patient and epidemiological factors associated with influenza testing in hospitalized adults with acute respiratory illnesses, 2016-2017 to 2019-2020
Dalton AF , Couture A , DeSilva MB , Irving SA , Gohil S , Rao S , Fink RV , Naleway AL , Guo Z , Sundaresan D , Birch RJ , Ball S , Zheng K , Ong TC , Reed C , Bozio CH . Open Forum Infect Dis 2023 10 (4) ofad162 BACKGROUND: Data are limited on influenza testing among adults with acute respiratory illness (ARI)-associated hospitalizations. We identified factors associated with influenza testing in adult ARI-associated hospitalizations across the 2016-2017 through 2019-2020 influenza seasons. METHODS: Using data from 4 health systems in the United States, we identified hospitalizations that had an ARI discharge diagnosis or respiratory virus test. A hospitalization with influenza testing was based on testing performed within 14 days before through 72 hours after admission. We used random forest analysis to identify patient characteristics and influenza activity indicators that were most important in terms of their relationship to influenza testing. RESULTS: Across 4 seasons, testing rates ranged from 14.8%-19.4% at 3 pooled sites and 60.1%-78.5% at a fourth site with different testing practices. Discharge diagnoses of pneumonia or infectious disease of noninfluenza etiology, presence of ARI signs/symptoms, hospital admission month, and influenza-like illness activity level were consistently among the variables with the greatest relative importance. CONCLUSIONS: Select ARI diagnoses and indicators of influenza activity were the most important factors associated with influenza testing among ARI-associated hospitalizations. Improved understanding of which patients are tested may enhance influenza burden estimates and allow for more timely clinical management of influenza-associated hospitalizations. |
Vaccine effectiveness against influenza-associated urgent care, emergency department, and hospital encounters during the 2021-2022 season, VISION Network
Tenforde MW , Weber ZA , DeSilva MB , Stenehjem E , Yang DH , Fireman B , Gaglani M , Kojima N , Irving SA , Rao S , Grannis SJ , Naleway AL , Kirshner L , Kharbanda AB , Dascomb K , Lewis N , Dalton AF , Ball SW , Natarajan K , Ong TC , Hartmann E , Embi PJ , McEvoy CE , Grisel N , Zerbo O , Dunne MM , Arndorfer J , Goddard K , Dickerson M , Patel P , Timbol J , Griggs EP , Hansen J , Thompson MG , Flannery B , Klein NP . J Infect Dis 2023 228 (2) 185-195 BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at three sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and SARS-CoV-2-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: 86,732 ED/UC ARI-associated encounters (7,696 [9%] cases) and 16,805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI): 20-29%) and 25% (95%CI: 11-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; CI: -5-17%) or with immunocompromising conditions (4%, CI:-45-36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE. |
Relationships between social vulnerability and COVID-19 vaccination coverage and vaccine effectiveness
Dalton AF , Weber ZA , Allen KS , Stenehjem E , Irving SA , Spark TL , Adams K , Zerbo O , Lazariu V , Dixon BE , Dascomb K , Hartmann E , Kharbanda AB , Ong TC , DeSilva MB , Beaton M , Gaglani M , Patel P , Naleway AL , Sam Kish MN , Grannis SJ , Grisel N , Sloan-Aagard C , Rao S , Raiyani C , Dickerson M , Bassett E , Fadel WF , Arndorfer J , Nanez J , Barron MA , Vazquez-Benitez G , Liao IC , Griggs EP , Reese SE , Valvi NR , Murthy K , Rowley EAK , Embi PJ , Ball S , Link-Gelles R , Tenforde MW . Clin Infect Dis 2023 76 (9) 1615-1625 BACKGROUND: COVID-19 vaccination coverage remains lower in communities with higher social vulnerability. Factors such as SARS-CoV-2 exposure risk and access to health care are often correlated with social vulnerability and may therefore contribute to a relationship between vulnerability and observed vaccine effectiveness (VE). Understanding whether these factors impact VE could contribute to our understanding of real-world VE. METHODS: We used electronic health record data from seven health systems to assess vaccination coverage among patients with medically attended COVID-19-like illness. We then used a test-negative design to assess VE for 2- and 3-dose mRNA adult (≥18 years) vaccine recipients across Social Vulnerability Index (SVI) quartiles. SVI rankings were determined by geocoding patient addresses to census tracts; rankings were grouped into quartiles for analysis. RESULTS: In July 2021, primary series vaccination coverage was higher in the least vulnerable quartile than in the most vulnerable quartile (56% vs. 36%, respectively). In February 2022, booster dose coverage among persons who had completed a primary series was higher in the least vulnerable quartile than in the most vulnerable quartile (43% vs. 30%). VE among 2-dose and 3-dose recipients during the Delta and Omicron BA.1 periods of predominance was similar across SVI quartiles. CONCLUSIONS: COVID-19 vaccination coverage varied substantially by SVI. Differences in VE estimates by SVI were minimal across groups after adjusting for baseline patient factors. However, lower vaccination coverage among more socially vulnerable groups means that the burden of illness is still disproportionately borne by the most socially vulnerable populations. |
Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022.
Natarajan K , Prasad N , Dascomb K , Irving SA , Yang DH , Gaglani M , Klein NP , DeSilva MB , Ong TC , Grannis SJ , Stenehjem E , Link-Gelles R , Rowley EA , Naleway AL , Han J , Raiyani C , Benitez GV , Rao S , Lewis N , Fadel WF , Grisel N , Griggs EP , Dunne MM , Stockwell MS , Mamawala M , McEvoy C , Barron MA , Goddard K , Valvi NR , Arndorfer J , Patel P , Mitchell PK , Smith M , Kharbanda AB , Fireman B , Embi PJ , Dickerson M , Davis JM , Zerbo O , Dalton AF , Wondimu MH , Azziz-Baumgartner E , Bozio CH , Reynolds S , Ferdinands J , Williams J , Schrag SJ , Verani JR , Ball S , Thompson MG , Dixon BE . MMWR Morb Mortal Wkly Rep 2022 71 (13) 495-502 CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome(†) (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network(§) determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits(¶) and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted. |
Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5-17 Years - VISION Network, 10 States, April 2021-January 2022.
Klein NP , Stockwell MS , Demarco M , Gaglani M , Kharbanda AB , Irving SA , Rao S , Grannis SJ , Dascomb K , Murthy K , Rowley EA , Dalton AF , DeSilva MB , Dixon BE , Natarajan K , Stenehjem E , Naleway AL , Lewis N , Ong TC , Patel P , Konatham D , Embi PJ , Reese SE , Han J , Grisel N , Goddard K , Barron MA , Dickerson M , Liao IC , Fadel WF , Yang DH , Arndorfer J , Fireman B , Griggs EP , Valvi NR , Hallowell C , Zerbo O , Reynolds S , Ferdinands J , Wondimu MH , Williams J , Bozio CH , Link-Gelles R , Azziz-Baumgartner E , Schrag SJ , Thompson MG , Verani JR . MMWR Morb Mortal Wkly Rep 2022 71 (9) 352-358 The efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine against laboratory-confirmed COVID-19 exceeded 90% in clinical trials that included children and adolescents aged 5-11, 12-15, and 16-17 years (1-3). Limited real-world data on 2-dose mRNA vaccine effectiveness (VE) in persons aged 12-17 years (referred to as adolescents in this report) have also indicated high levels of protection against SARS-CoV-2 (the virus that causes COVID-19) infection and COVID-19-associated hospitalization (4-6); however, data on VE against the SARS-CoV-2 B.1.1.529 (Omicron) variant and duration of protection are limited. Pfizer-BioNTech VE data are not available for children aged 5-11 years. In partnership with CDC, the VISION Network* examined 39,217 emergency department (ED) and urgent care (UC) encounters and 1,699 hospitalizations(†) among persons aged 5-17 years with COVID-19-like illness across 10 states during April 9, 2021-January 29, 2022,(§) to estimate VE using a case-control test-negative design. Among children aged 5-11 years, VE against laboratory-confirmed COVID-19-associated ED and UC encounters 14-67 days after dose 2 (the longest interval after dose 2 in this age group) was 46%. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 83% and 76%, respectively; VE ≥150 days after dose 2 was 38% and 46%, respectively. Among adolescents aged 16-17 years, VE increased to 86% ≥7 days after dose 3 (booster dose). VE against COVID-19-associated ED and UC encounters was substantially lower during the Omicron predominant period than the B.1.617.2 (Delta) predominant period among adolescents aged 12-17 years, with no significant protection ≥150 days after dose 2 during Omicron predominance. However, in adolescents aged 16-17 years, VE during the Omicron predominant period increased to 81% ≥7 days after a third booster dose. During the full study period, including pre-Delta, Delta, and Omicron predominant periods, VE against laboratory-confirmed COVID-19-associated hospitalization among children aged 5-11 years was 74% 14-67 days after dose 2, with wide CIs that included zero. Among adolescents aged 12-15 and 16-17 years, VE 14-149 days after dose 2 was 92% and 94%, respectively; VE ≥150 days after dose 2 was 73% and 88%, respectively. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations, including a booster dose for those aged 12-17 years. |
Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance - VISION Network, 10 States, August 2021-January 2022.
Ferdinands JM , Rao S , Dixon BE , Mitchell PK , DeSilva MB , Irving SA , Lewis N , Natarajan K , Stenehjem E , Grannis SJ , Han J , McEvoy C , Ong TC , Naleway AL , Reese SE , Embi PJ , Dascomb K , Klein NP , Griggs EP , Konatham D , Kharbanda AB , Yang DH , Fadel WF , Grisel N , Goddard K , Patel P , Liao IC , Birch R , Valvi NR , Reynolds S , Arndorfer J , Zerbo O , Dickerson M , Murthy K , Williams J , Bozio CH , Blanton L , Verani JR , Schrag SJ , Dalton AF , Wondimu MH , Link-Gelles R , Azziz-Baumgartner E , Barron MA , Gaglani M , Thompson MG , Fireman B . MMWR Morb Mortal Wkly Rep 2022 71 (7) 255-263 CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance(†) (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites(§) examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates).(¶) Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits. |
Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years - United States, August 2020-August 2021.
Siegel DA , Reses HE , Cool AJ , Shapiro CN , Hsu J , Boehmer TK , Cornwell CR , Gray EB , Henley SJ , Lochner K , Suthar AB , Lyons BC , Mattocks L , Hartnett K , Adjemian J , van Santen KL , Sheppard M , Soetebier KA , Logan P , Martin M , Idubor O , Natarajan P , Sircar K , Oyegun E , Dalton J , Perrine CG , Peacock G , Schweitzer B , Morris SB , Raizes E . MMWR Morb Mortal Wkly Rep 2021 70 (36) 1249-1254 Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,(†) causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness. |
Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes.
Voss WN , Hou YJ , Johnson NV , Delidakis G , Kim JE , Javanmardi K , Horton AP , Bartzoka F , Paresi CJ , Tanno Y , Chou CW , Abbasi SA , Pickens W , George K , Boutz DR , Towers DM , McDaniel JR , Billick D , Goike J , Rowe L , Batra D , Pohl J , Lee J , Gangappa S , Sambhara S , Gadush M , Wang N , Person MD , Iverson BL , Gollihar JD , Dye J , Herbert A , Finkelstein IJ , Baric RS , McLellan JS , Georgiou G , Lavinder JJ , Ippolito GC . Science 2021 372 (6546) 1108-1112 The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma following SARS-CoV-2 infection are unknown. Proteomic deconvolution of the IgG repertoire to the spike glycoprotein in convalescent subjects revealed that the response is directed predominantly (>80%) against epitopes residing outside the receptor-binding domain (RBD). In one subject, just four IgG lineages accounted for 93.5% of the response, including an N-terminal domain (NTD)-directed antibody that was protective against lethal viral challenge. Genetic, structural, and functional characterization of a multi-donor class of "public" antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern. These data show that "public" NTD-directed and other non-RBD plasma antibodies are prevalent and have implications for SARS-CoV-2 protection and antibody escape. |
Towards Unified Data Exchange Formats for Reporting Molecular Drug Susceptibility Testing.
Bonney W , Price SF , Abhyankar S , Merrick R , Hampole V , Halse TA , DiDonato C , Dalton T , Metchock B , Starks AM , Miramontes R . Online J Public Health Inform 2020 12 (2) e14 BACKGROUND: With the rapid development of new advanced molecular detection methods, identification of new genetic mutations conferring pathogen resistance to an ever-growing variety of antimicrobial substances will generate massive genomic datasets for public health and clinical laboratories. Keeping up with specialized standard coding for these immense datasets will be extremely challenging. This challenge prompted our effort to create a common molecular resistance Logical Observation Identifiers Names and Codes (LOINC) panel that can be used to report any identified antimicrobial resistance pattern. OBJECTIVE: To develop and utilize a common molecular resistance LOINC panel for molecular drug susceptibility testing (DST) data exchange in the U.S. National Tuberculosis Surveillance System using California Department of Public Health (CDPH) and New York State Department of Health as pilot sites. METHODS: We developed an interface and mapped incoming molecular DST data to the common molecular resistance LOINC panel using Health Level Seven (HL7) v2.5.1 Electronic Laboratory Reporting (ELR) message specifications through the Orion Health™ Rhapsody Integration Engine v6.3.1. RESULTS: Both pilot sites were able to process and upload/import the standardized HL7 v2.5.1 ELR messages into their respective systems; albeit CDPH identified areas for system improvements and has focused efforts to streamline the message importation process. Specifically, CDPH is enhancing their system to better capture parent-child elements and ensure that the data collected can be accessed seamlessly by the U.S. Centers for Disease Control and Prevention. DISCUSSION: The common molecular resistance LOINC panel is designed to be generalizable across other resistance genes and ideally also applicable to other disease domains. CONCLUSION: The study demonstrates that it is possible to exchange molecular DST data across the continuum of disparate healthcare information systems in integrated public health environments using the common molecular resistance LOINC panel. |
Molecular evaluation of fluoroquinolone resistance in serial Mycobacterium tuberculosis isolates from individuals diagnosed with multidrug-resistant tuberculosis.
Willby M , Chopra P , Lemmer D , Klein K , Dalton TL , Engelthaler DM , Cegielski P , Posey JE . Antimicrob Agents Chemother 2020 65 (1) Fluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Varying levels of resistance are associated with specific mutations within the Quinolone Resistance Determining Region (QRDR) of gyrA We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PETTS) with baseline (FQ(R)) or acquired FQ resistance (FQ(ACQR)) using the IonTorrent™ Personal Genome Machine to a depth of 10,000x and reported single nucleotide polymorphisms in ≥1% of reads. FQ(R) isolates harbored 15 distinct alleles with 1.3 (max=6) on average per isolate. Eighteen alleles were identified in FQ(ACQR) isolates with an average of 1.6 (max=9) per isolate. Isolates from 78% of FQ(ACQR) individuals had mutant alleles identified within 6 months of treatment initiation. Asp94Gly followed by Ala90Val were the predominant alleles in initial FQ-resistant isolates. Seventy-seven percent (36/47) of FQ(ACQR) group patients had isolates with FQ resistance alleles prior to changes to the FQ component of their treatment. Unlike individuals treated initially with other FQs, none of the 21 individuals treated initially with levofloxacin developed genotypic or phenotypic FQ resistance, although, country of residence is likely a contributing factor since 69% of these individuals were from a single country. Initial detection of phenotypic and genotypic resistance occurred simultaneously for most; however, phenotypic resistance occurred earlier in isolates harboring mixtures of very low-abundance (<1% of reads) alleles while genotypic resistance often occurred earlier for low-level resistance-associated alleles. Understanding factors influencing acquisition and evolution of FQ resistance could reveal strategies for improved treatment success. |
Cytomegalovirus and Epstein-Barr virus viremia are associated with HIV DNA levels in the reservoir of Kenyan infants on antiretroviral therapy.
Slyker JA , Guthrie B , Pankau M , Tapia K , Wamalwa D , Benki-Nugent S , Ngugi E , Huang ML , Njuguna I , Langat A , John-Stewart G , Lehman D . J Infect Dis 2020 223 (11) 1923-1927 Identifying determinants of HIV reservoir levels may inform novel viral eradication strategies. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections were assessed as predictors of HIV proviral DNA level in 26 HIV RNA-suppressed Kenyan children starting antiretroviral therapy (ART) before 7 months of age. Earlier acquisition of CMV and EBV, and higher cumulative burden of systemic EBV DNA viremia were each associated with higher HIV DNA level in the reservoir after 24 months of ART, independent of HIV RNA levels over time. These data suggest delaying or containing CMV and EBV viremia may be novel strategies to limit HIV reservoir formation. |
Isoniazid- and Rifampin-Resistance Mutations Associated with Resistance to Second-line Drugs and with Sputum Culture Conversion.
Click ES , Kurbatova E , Alexander H , Dalton TL , Chen MP , Posey JE , Ershova JJ , Cegielski P . J Infect Dis 2020 221 (12) 2072-2082 BACKGROUND: Mutations in the genes inhA, katG and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. METHODS: In a multi-country prospective cohort study of MDR-TB, we identified inhA, katG and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time-to-sputum-culture-conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. RESULTS: In total, 447 participants enrolled January 2005-December 2008 from seven countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance.Relative to mutation of katG only, mutation of inhA promoter and katG was associated with increased acquired fluoroquinolone resistance and slower TSCC (125.5 vs. 89.0 days). CONCLUSIONS: Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile. |
Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA Clinical Practice Guideline
Nahid P , Mase SR , Migliori GB , Sotgiu G , Bothamley GH , Brozek JL , Cattamanchi A , Cegielski JP , Chen L , Daley CL , Dalton TL , Duarte R , Fregonese F , Horsburgh CR Jr , Ahmad Khan F , Kheir F , Lan Z , Lardizabal A , Lauzardo M , Mangan JM , Marks SM , McKenna L , Menzies D , Mitnick CD , Nilsen DM , Parvez F , Peloquin CA , Raftery A , Schaaf HS , Shah NS , Starke JR , Wilson JW , Wortham JM , Chorba T , Seaworth B . Am J Respir Crit Care Med 2019 200 (10) e93-e142 Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB. |
Detection of Bacillus anthracis in animal tissues using InBios Active Anthrax Detect Rapid Test lateral flow immunoassay
Kolton CB , Marston CK , Stoddard RA , Cossaboom C , Salzer JS , Kozel TR , Gates-Hollingsworth MA , Cleveland CA , Thompson AT , Dalton MF , Yabsley MJ , Hoffmaster AR . Lett Appl Microbiol 2019 68 (6) 480-484 The Active Anthrax Detect (AAD) Rapid Test lateral flow immunoassay is a point-of-care assay that was under investigational use for detecting Bacillus anthracis capsular polypeptide (polyglutamic acid) in human blood, serum, and plasma. Small sample volumes, rapid results, and no refrigeration required allow for easy use in either the field or laboratory. Although the test was developed for use in suspect cases of human inhalation anthrax, its features also make it a potentially powerful tool for testing suspect animal cases. We tested animal tissue samples that were confirmed or ruled out for B. anthracis. The AAD Rapid Tests were also deployed in the field, testing animal carcasses during an anthrax outbreak in hippopotami (Hippopotamus amphibius) and Cape buffalo (Syncerus caffer) in Namibia. Evaluation of all samples showed a specificity of 82% and sensitivity of 98%. However, when the assay was used on specimens from only fresh carcasses (dead for less than 24 hours), the specificity increased to 96%. The AAD Rapid Test is a rapid and simple screening assay, but confirmatory testing needs to be done, especially when the age of the sample (days animal has been deceased) is unknown. This article is protected by copyright. All rights reserved. |
Exploring the science, safety, and benefits of air care products: perspectives from the inaugural air care summit
Johnson MB , Kingston R , Utell MJ , Wells JR , Singal M , Troy WR , Horenziak S , Dalton P , Ahmed FK , Herz RS , Osimitz TG , Prawer S , Yin S . Inhal Toxicol 2019 31 (1) 1-13 Seventy-one percent of US households purchase air care products. Air care products span a diverse range of forms, including scented aerosol sprays, pump sprays, diffusers, gels, candles, and plug-ins. These products are used to eliminate indoor malodors and to provide pleasant scent experiences. The use of air care products can lead to significant benefits as studies have shown that indoor malodor can cause adverse effects, negatively impacting quality of life, hygiene, and the monetary value of homes and cars, while disproportionately affecting lower income populations. Additionally, studies have also shown that scent can have positive benefits related to mood, stress reduction, and memory enhancement among others. Despite the positive benefits associated with air care products, negative consumer perceptions regarding the safety of air care products can be a barrier to their use. During the inaugural Air Care Summit, held on 18 May 2018 in the Washington, DC, metropolitan area, multidisciplinary experts including industry stakeholders, academics, and scientific and medical experts were invited to share and assess the existing data related to air care products, focusing on ingredient and product safety and the benefits of malodor removal and scent. At the Summit's completion, a panel of independent experts representing the fields of pulmonary medicine, medical and clinical toxicology, pediatric toxicology, basic science toxicology, occupational dermatology and experimental psychology convened to review the data presented, identify potential knowledge gaps, and suggest future research directions to further assess the safety and benefits of air care products. |
Validation of novel Mycobacterium tuberculosis isoniazid resistance mutations not detectable by common molecular tests.
Kandler JL , Mercante AD , Dalton TL , Ezewudo MN , Cowan LS , Burns SP , Metchock B , Cegielski P , Posey JE . Antimicrob Agents Chemother 2018 62 (10) Resistance to the first-line anti-tuberculosis (TB) drug, isoniazid (INH), is widespread, and the mechanism of resistance is unknown in approximately 15% of INH-resistant (INH-R) strains. To improve molecular detection of INH-R TB, we used whole genome sequencing (WGS) to analyze 52 phenotypically INH-R Mycobacterium tuberculosis complex (MTBC) clinical isolates that lacked the common katG S315T or inhA promoter mutations. Approximately 94% (49/52) of strains had mutations at known INH-associated loci that were likely to confer INH resistance. All such mutations would be detectable by sequencing more DNA adjacent to existing target regions. Use of WGS minimized the chances of missing infrequent INH resistance mutations outside commonly targeted hotspots. We used recombineering to generate 12 observed clinical katG mutations in the pansusceptible H37Rv reference strain and determined their impact on INH resistance. Our functional genetic experiments have confirmed the role of seven suspected INH resistance mutations and discovered five novel INH resistance mutations. All recombineered katG mutations conferred resistance to INH at a minimum inhibitory concentration of >/=0.25 mug/mL and should be added to the list of INH resistance determinants targeted by molecular diagnostic assays. We conclude that WGS is a useful tool for detecting uncommon INH resistance mutations that would otherwise be missed by current targeted molecular testing methods, and suggest that its use (or use of expanded conventional or NGS-based targeted sequencing) may provide earlier diagnosis of INH-R TB. |
Initial public health laboratory response after Hurricane Maria - Puerto Rico, 2017
Concepcion-Acevedo J , Patel A , Luna-Pinto C , Pena RG , Cuevas Ruiz RI , Arbolay HR , Toro M , Deseda C , De Jesus VR , Ribot E , Gonzalez JQ , Rao G , De Leon Salazar A , Ansbro M , White BB , Hardy MC , Georgi JC , Stinnett R , Mercante AM , Lowe D , Martin H , Starks A , Metchock B , Johnston S , Dalton T , Joglar O , Stafford C , Youngblood M , Klein K , Lindstrom S , Berman L , Galloway R , Schafer IJ , Walke H , Stoddard R , Connelly R , McCaffery E , Rowlinson MC , Soroka S , Tranquillo DT , Gaynor A , Mangal C , Wroblewski K , Muehlenbachs A , Salerno RM , Lozier M , Sunshine B , Shapiro C , Rose D , Funk R , Pillai SK , O'Neill E . MMWR Morb Mortal Wkly Rep 2018 67 (11) 333-336 Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services. |
A multistate outbreak of human Salmonella agona infections associated with consumption of fresh, whole papayas imported from Mexico - United States, 2011
Mba-Jonas A , Culpepper W , Hill T , Cantu V , Loera J , Borders J , Saathoff-Huber L , Nsubuga J , Zambrana I , Dalton S , Williams I , Neil KP . Clin Infect Dis 2018 66 (11) 1756-1761 Background: Nontyphoidal Salmonella causes ~1 million food-borne infections annually in the United States. We began investigating a multistate outbreak of Salmonella serotype Agona infections in April 2011. Methods: A case was defined as infection with the outbreak strain of Salmonella Agona occurring between 1 January and 25 August 2011. We developed hypotheses through iterative interviews. Product distribution analyses and traceback investigations were conducted. The Food and Drug Administration (FDA) tested papayas from Mexico for Salmonella. Results: We identified 106 case patients from 25 states. Their median age was 21 years (range, 1-91). Thirty-nine of 61 case patients (64%) reported Hispanic/Latino ethnicity; 11 of 65 (17%) travelled to Mexico before illness. Thirty-two of 56 case patients (57%) reported papaya consumption. Distribution analyses revealed that three firms, including Distributor A, distributed papaya to geographic areas that aligned with both the location and timing of illnesses. Traceback of papayas purchased by ill persons in four states identified Distributor A as the common supplier. FDA testing isolated the outbreak strain from a papaya sample collected at distributor A and from another sample collected at the US-Mexico border, destined for distributor A. FDA isolated Salmonella species from 62 of 388 papaya import samples (16%). The investigation led to a recall of fresh, whole papayas from Distributor A and an FDA import alert for all papayas from Mexico. Conclusions: This is the first reported Salmonella outbreak in the United States linked to fresh, whole papayas. The outbreak highlights important issues regarding the safety of imported produce. |
The use of a shared services model for mycobacteriology testing: Lessons learned
Stafford C , Atkinson-Dunn R , Buss SN , Dalton T , Gibson D , Johnston S , King E , Grace Lin SY , Mitchell KK , Murtaugh WA , Sease H , Southern TR , Tans-Kersten JL , Travanty EA , Triplett LR , Wroblewski K , Starks AM . Public Health Rep 2017 133 (1) 33354917743498 OBJECTIVES: Public health laboratories (PHLs) provide essential services in the diagnosis and surveillance of diseases of public health concern, such as tuberculosis. Maintaining access to high-quality laboratory testing is critical to continued disease detection and decline of tuberculosis cases in the United States. We investigated the practical experience of sharing tuberculosis testing services between PHLs through the Shared Services Project. METHODS: The Shared Services Project was a 9-month-long project funded through the Association of Public Health Laboratories and the Centers for Disease Control and Prevention during 2012-2013 as a one-time funding opportunity to consortiums of PHLs that proposed collaborative approaches to sharing tuberculosis laboratory services. Submitting PHLs maintained testing while simultaneously sending specimens to reference laboratories to compare turnaround times. RESULTS: During the 9-month project period, 107 Mycobacterium tuberculosis complex submissions for growth-based drug susceptibility testing and molecular detection of drug resistance testing occurred among the 3 consortiums. The median transit time for all submissions was 1.0 day. Overall, median drug susceptibility testing turnaround time (date of receipt in submitting laboratory to result) for parallel testing performed in house by submitting laboratories was 31.0 days; it was 43.0 days for reference laboratories. The median turnaround time for molecular detection of drug resistance results was 1.0 day (mean = 2.8; range, 0-14) from specimen receipt at the reference laboratories. CONCLUSIONS: The shared services model holds promise for specialized tuberculosis testing. Sharing of services requires a balance among quality, timeliness, efficiency, communication, and fiscal costs. |
Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study
Sharma A , Hill A , Kurbatova E , van der Walt M , Kvasnovsky C , Tupasi TE , Caoili JC , Gler MT , Volchenkov GV , Kazennyy BY , Demikhova OV , Bayona J , Contreras C , Yagui M , Leimane V , Cho SN , Kim HJ , Kliiman K , Akksilp S , Jou R , Ershova J , Dalton T , Cegielski P . Lancet Infect Dis 2017 17 (7) 707-715 BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5% (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. |
Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters
Cavanaugh JS , Jou R , Wu MH , Dalton T , Kurbatova E , Ershova J , Cegielski JP . J Antimicrob Chemother 2017 72 (6) 1678-1687 Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation. |
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