Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 85 Records) |
Query Trace: Sheth M[original query] |
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HIV replication under high-level cabotegravir is associated with the appearance of 3'-PPT mutations, circular DNA transcription and recombination
Wei X , Lipscomb JT , Tino AS , Cong ME , Ruone S , Bentz ML , Sheth M , Garcia-Lerma G , Johnson JA . Viruses 2024 16 (12) ![]() ![]() The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB. HIV-1IIIB was cultured in paired experiments of continuous high (300 nM) CAB initiated 2 h or 24 h after infection. After eight months of CAB treatment, no int resistance was detected. Conversely, HIV RNA 3'-PPT mutants were detected within one month and were the majority virus by day 98. The appearance of 3'-PPT variants coincided with a rapid accumulation of HIV 1-LTR and 2-LTR circles. RNA amplification from the 3'-LTR TAR identified transcripts crossing 2-LTR circle junctions, which incorporated the adjacent U5 sequence identical to the 3'-PPT mutants. 3'-PPT variants were only identified in LTR circles and transcripts. Additionally, we found evidence of linear HIV and LTR circle recombination with human DNA at motifs homologous to 3'-PPT sequences. HIV persistence under CAB was associated with transcription and recombination of LTR circle sequences. |
Genomic surveillance for SARS-CoV-2 variants: Circulation of Omicron XBB and JN.1 lineages - United States, May 2023-September 2024
Ma KC , Castro J , Lambrou AS , Rose EB , Cook PW , Batra D , Cubenas C , Hughes LJ , MacCannell DR , Mandal P , Mittal N , Sheth M , Smith C , Winn A , Hall AJ , Wentworth DE , Silk BJ , Thornburg NJ , Paden CR . MMWR Morb Mortal Wkly Rep 2024 73 (42) 938-945 ![]() ![]() CDC continues to track the evolution of SARS-CoV-2, including the Omicron variant and its descendants, using national genomic surveillance. This report summarizes U.S. trends in variant proportion estimates during May 2023-September 2024, a period when SARS-CoV-2 lineages primarily comprised descendants of Omicron variants XBB and JN.1. During summer and fall 2023, multiple descendants of XBB with immune escape substitutions emerged and reached >10% prevalence, including EG.5-like lineages by June 24, FL.1.5.1-like lineages by August 5, HV.1 lineage by September 30, and HK.3-like lineages by November 11. In winter 2023, the JN.1 variant emerged in the United States and rapidly attained predominance nationwide, representing a substantial genetic shift (>30 spike protein amino acid differences) from XBB lineages. Descendants of JN.1 subsequently circulated and reached >10% prevalence, including KQ.1-like and KP.2-like lineages by April 13, KP.3 and LB.1-like lineages by May 25, and KP.3.1.1 by July 20. Surges in COVID-19 cases occurred in winter 2024 during the shift to JN.1 predominance, as well as in summer 2023 and 2024 during circulation of multiple XBB and JN.1 descendants, respectively. The ongoing evolution of the Omicron variant highlights the importance of continued genomic surveillance to guide medical countermeasure development, including the selection of antigens for updated COVID-19 vaccines. |
Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant
Beall B , Chochua S , Metcalf B , Lin W , Tran T , Li Z , Li Y , Bentz ML , Sheth M , Osis G , McGee L . J Infect Dis 2024 ![]() ![]() BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant. |
The frequency and function of nucleoprotein-specific CD8(+) T cells are critical for heterosubtypic immunity against influenza virus infection
Amoah S , Cao W , Sayedahmed EE , Wang Y , Kumar A , Mishina M , Eddins DJ , Wang WC , Burroughs M , Sheth M , Lee J , Shieh WJ , Ray SD , Bohannon CD , Ranjan P , Sharma SD , Hoehner J , Arthur RA , Gangappa S , Wakamatsu N , Johnston HR , Pohl J , Mittal SK , Sambhara S . J Virol 2024 e0071124 ![]() Cytotoxic T lymphocytes (CTLs) mediate host defense against viral and intracellular bacterial infections and tumors. However, the magnitude of CTL response and their function needed to confer heterosubtypic immunity against influenza virus infection are unknown. We addressed the role of CD8(+) T cells in the absence of any cross-reactive antibody responses to influenza viral proteins using an adenoviral vector expressing a 9mer amino acid sequence recognized by CD8(+) T cells. Our results indicate that both CD8(+) T cell frequency and function are crucial for heterosubtypic immunity. Low morbidity, lower viral lung titers, low to minimal lung pathology, and better survival upon heterosubtypic virus challenge correlated with the increased frequency of NP-specific CTLs. NP-CD8(+) T cells induced by differential infection doses displayed distinct RNA transcriptome profiles and functional properties. CD8(+) T cells induced by a high dose of influenza virus secreted significantly higher levels of IFN-γ and exhibited higher levels of cytotoxic function. The mice that received NP-CD8(+) T cells from the high-dose virus recipients through adoptive transfer had lower viral titers following viral challenge than those induced by the low dose of virus, suggesting differential cellular programming by antigen dose. Enhanced NP-CD8(+) T-cell functions induced by a higher dose of influenza virus strongly correlated with the increased expression of cellular and metabolic genes, indicating a shift to a more glycolytic metabolic phenotype. These findings have implications for developing effective T cell vaccines against infectious diseases and cancer. IMPORTANCE: Cytotoxic T lymphocytes (CTLs) are an important component of the adaptive immune system that clears virus-infected cells or tumor cells. Hence, developing next-generation vaccines that induce or recall CTL responses against cancer and infectious diseases is crucial. However, it is not clear if the frequency, function, or both are essential in conferring protection, as in the case of influenza. In this study, we demonstrate that both CTL frequency and function are crucial for providing heterosubtypic immunity to influenza by utilizing an Ad-viral vector expressing a CD8 epitope only to rule out the role of antibodies, single-cell RNA-seq analysis, as well as adoptive transfer experiments. Our findings have implications for developing T cell vaccines against infectious diseases and cancer. |
Coronavirus Disease 2019 (COVID-19) vaccination and stillbirth in the Vaccine Safety Datalink
Denoble AE , Vazquez-Benitez G , Sheth SS , Ackerman-Banks CM , DeSilva MB , Zhu J , Daley MF , Getahun D , Klein NP , Vesco KK , Irving SA , Nelson J , Williams JTB , Hambidge SJ , Donahue JG , Weintraub ES , Kharbanda EO , Lipkind HS . Obstet Gynecol 2024 OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. METHODS: We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. RESULTS: In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). CONCLUSION: No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy. |
Antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S. Throughout the Delta to Omicron waves
Di H , Pusch EA , Jones J , Kovacs NA , Hassell N , Sheth M , Lynn KS , Keller MW , Wilson MM , Keong LM , Cui D , Park SH , Chau R , Lacek KA , Liddell JD , Kirby MK , Yang G , Johnson M , Thor S , Zanders N , Feng C , Surie D , DeCuir J , Lester SN , Atherton L , Hicks H , Tamin A , Harcourt JL , Coughlin MM , Self WH , Rhoads JP , Gibbs KW , Hager DN , Shapiro NI , Exline MC , Lauring AS , Rambo-Martin B , Paden CR , Kondor RJ , Lee JS , Barnes JR , Thornburg NJ , Zhou B , Wentworth DE , Davis CT . Vaccines (Basel) 2024 12 (5) ![]() ![]() Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates. |
Neurovascular complications of iatrogenic fusarium solani meningitis
Strong N , Meeks G , Sheth SA , McCullough L , Villalba JA , Tan C , Barreto A , Wanger A , McDonald M , Kan P , Shaltoni H , Campo Maldonado J , Parada V , Hassan AE , Reagan-Steiner S , Chiller T , Gold JAW , Smith DJ , Ostrosky-Zeichner L . N Engl J Med 2024 390 (6) 522-529 A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days. |
Correction for Weigand et al., Complete Genome Sequences of Two Bordetella hinzii Strains Isolated from Humans.
Weigand MR , Changayil S , Kulasekarapandian Y , Batra D , Loparev V , Juieng P , Rowe L , Sheth M , Davis JK , Tondella ML . Genome Announc 2016 4 (1) ![]() Volume 3, no. 4, e00965-15, 2015. Page 1: The byline and affiliation line should read as given above. |
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Keller MW , Keong LM , Rambo-Martin BL , Hassell N , Lacek KA , Wilson MM , Kirby MK , Liddell J , Owuor DC , Sheth M , Madden J , Lee JS , Kondor RJ , Wentworth DE , Barnes JR . Microbiol Spectr 2023 e0298223 ![]() ![]() The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection. |
Invasive nontypeable haemophilus influenzae disease outbreak at an elementary school - Michigan, May 2023
Weinberg MM , Akel K , Akinyemi O , Balasubramanian T , Blankenship HM , Collins JP , Collins J , Henderson T , Johnson S , Lai J , McNamara LA , Richardson C , Sharma S , Sheth D . MMWR Morb Mortal Wkly Rep 2024 73 (32) 691-695 In May 2023, the Detroit Health Department was notified of four cases of invasive nontypeable Haemophilus influenzae (Hi) disease among students attending the same elementary school and grade, all with illness onsets within 7 days. Three patients were hospitalized, and one died. Most U.S. cases of invasive Hi disease are caused by nontypeable strains. No vaccines against nontypeable or non-type b Hi strains are currently available. Chemoprophylaxis is not typically recommended in response to nontypeable Hi cases; however, because of the high attack rate (four cases among 46 students; 8.7%), rifampin prophylaxis was recommended for household contacts of patients with confirmed cases and for all students and staff members in the school wing where confirmed cases occurred. Only 10.8% of students for whom chemoprophylaxis was recommended took it, highlighting gaps in understanding among caregivers and health care providers about persons for whom chemoprophylaxis was recommended. Public health authorities subsequently enhanced communication and education to the school community, improved coordination with health care partners, and established mass prophylaxis clinics at the school. This outbreak highlights the potential for nontypeable Hi to cause serious illness and outbreaks and the need for chemoprophylaxis guidance for nontypeable Hi disease. Achieving high chemoprophylaxis coverage requires education, communication, and coordination with community and health care partners. |
Western Kenyan Anopheles gambiae s.s. showing intense permethrin resistance harbor distinct microbiota (preprint)
Omoke D , Kipsum M , Otieno S , Esalimba E , Sheth M , Lenhart A , Njeru EM , Ochomo E , Dada N . bioRxiv 2020 2020.11.12.378760 Background Insecticide resistance poses a growing challenge to malaria vector control in Kenya and around the world. Following evidence of associations between the mosquito microbiota and insecticide resistance, we comparatively characterized the microbiota of An. gambiae s.s. from Tulukuyi village, Bungoma, Kenya, with differing permethrin resistance profiles.Methods Using the CDC bottle bioassay, 133 2-3 day-old, virgin, non-blood fed female F1 progeny of field-caught An. gambiae s.s. were exposed to five times (107.5μg/ml) the discriminating dose of permethrin. Post bioassay, 50 resistant and 50 susceptible mosquitoes were subsequently screened for kdr East and West mutations, and individually processed for microbial analysis using high throughput sequencing targeting the universal bacterial and archaeal 16S rRNA gene.Results 47% of the samples tested (n=133) were resistant, and of the 100 selected for further processing, 99% were positive for kdr East and 1% for kdr West. Overall, 84 bacterial taxa were detected across all mosquito samples, with 36 of these shared between resistant and susceptible mosquitoes. A total of 20 were unique to the resistant mosquitoes and 28 were unique to the susceptible mosquitoes. There were significant differences in bacterial composition between resistant and susceptible individuals (F=2.33, P=0.001), with presence of Sphingobacterium, Lysinibacillus and Streptococcus (all known pyrethroid-degrading taxa), and the radiotolerant Rubrobacter, being significantly associated with resistant mosquitoes. On the other hand, the presence of Myxococcus, was significantly associated with susceptible mosquitoes.Conclusion This is the first report of distinct microbiota in An. gambiae s.s. associated with intense pyrethroid resistance. The findings highlight differentially abundant bacterial taxa between resistant and susceptible mosquitoes, and further suggest a microbe-mediated mechanism of insecticide resistance in mosquitoes. Our results also indicate fixation of the kdr East mutation in this mosquito population, precluding further analysis of its associations with the mosquito microbiota, but presenting the hypothesis that any microbe-mediated mechanism of insecticide resistance would be likely of a metabolic nature. Overall, this study lays initial groundwork for understanding microbe-mediated mechanisms of insecticide resistance in African malaria vectors, and potentially identifying novel microbial markers of insecticide resistance that could supplement existing vector surveillance tools.Competing Interest StatementThe authors have declared no competing interest. |
Geographic heterogeneity in Anopheles albimanus microbiota is lost within one generation of laboratory colonization (preprint)
Dada N , Benedict AC , López F , Lol JC , Sheth M , Dzuris N , Padilla N , Lenhart A . bioRxiv 2020 2020.06.02.129619 Research on mosquito-microbe interactions may lead to new tools for mosquito and mosquito-borne disease control. To date, such research has largely utilized laboratory-reared mosquitoes that may lack the microbial diversity of wild populations. To better understand how mosquito microbiota may vary across different geographic locations and upon laboratory colonization, we characterized the microbiota of F1 progeny of wild-caught adult Anopheles albimanus from four locations in Guatemala using high throughput 16S rRNA amplicon sequencing. A total of 132 late instar larvae and 135 2-5day old, non-blood-fed virgin adult females were reared under identical laboratory conditions, pooled (3 individuals/pool) and analyzed. Larvae from mothers collected at different sites showed different microbial compositions (p=0.001; F = 9.5), but these differences were no longer present at the adult stage (p=0.12; F = 1.6). This indicates that mosquitoes retain a significant portion of their field-derived microbiota throughout immature development but shed them before or during adult eclosion. This is the first time the microbiota of F1 progeny of wild-caught mosquitoes has been characterized in relation to parental collection site, and our findings provide evidence that geographically associated heterogeneity in microbiota composition persists for a single generation, but only until the end of the larval stage. These findings advance our understanding of how the mosquito microbiota is altered upon first laboratory colonization, and raises considerations for how mosquito microbiome research may be extended beyond the laboratory to field settings.Competing Interest StatementThe authors have declared no competing interest. |
Pyrethroid exposure alters Anopheles albimanus microbiota and resistant mosquitoes harbor more insecticide-metabolizing bacteria (preprint)
Dada N , Lol JC , Benedict AC , Lopez F , Sheth M , Dzuris N , Padilla N , Lenhart A . bioRxiv 2019 537480 A deeper understanding of the mechanisms underlying insecticide resistance is needed to mitigate its threat to malaria vector control. Building upon our earlier identified associations between mosquito microbiota and insecticide resistance, we demonstrate for the first time, type-specific effects of pyrethroid exposure on internal and cuticle surface bacteria in adult progeny of field-collected Anopheles albimanus. In contrast, larval cuticle surface—but not internal—bacteria were affected by pyrethroid exposure. Being over five-folds more abundant in pyrethroid resistant adults, as compared to susceptible or non-insecticide-exposed mosquitoes, Klebsiella (alphacypermethrin), Pantoea and Asaia (permethrin) were identified as potential markers of pyrethroid resistance in An. albimanus. We also show for the first time that An. albimanus larvae and adult cuticles harbor more diverse bacterial communities than their internal microbial niches. Our findings indicate insecticide selection pressures on mosquito microbiota, and support the hypothesis of an undescribed microbe-mediated mechanism of insecticide metabolism in mosquitoes. |
Memory CD4 T cell subset organization in the female reproductive tract is regulated via the menstrual cycle through CCR5 signaling (preprint)
Swaims-Kohlmeier A , Wein AN , Hardnett FP , Sheth AN , Li ZRT , Williams ME , Radzio-Basu J , Zheng H , Dinh C , Haddad LB , Collins EMB , Lobby JL , Kost K , Hayward SL , Ofotokun I , Antia R , Scharer CD , Lowen AC , Garcia-Lerma JG , Kohlmeier JE . bioRxiv 2022 03 Despite their importance for immunity against sexually transmitted infections (STIs), the composition of the female reproductive tract (FRT) memory CD4 T cell population in response to changes in the local tissue environment during the menstrual cycle remains poorly defined. Here we show that across humans, non-human primates (NHP), and mice, FRT CD4 T cells comprise distinct subsets corresponding to migratory memory (TMM) and resident memory (TRM) cells. TMM display tissue-itinerant trafficking characteristics, restricted FRT tissue distribution, with distinct transcriptional properties and effector responses to infection. CD4 T cell subset fluctuations synchronized with cycle-driven proinflammatory changes within the local tissue environment and oral administration of a CCR5 antagonist inhibited cycle phase-specific migratory T cell surveillance. This study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of memory T cell defense at the site of STI exposure. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA (preprint)
Gigante CM , Plumb M , Ruprecht A , Zhao H , Wicker V , Wilkins K , Matheny A , Khan T , Davidson W , Sheth M , Burgin A , Burroughs M , Padilla J , Lee JS , Batra D , Hetrick EE , Howard DT , Garfin J , Tate L , Hubsmith SJ , Mendoza RM , Stanek D , Gillani S , Lee M , Mangla A , Blythe D , SierraPatev S , Carpenter-Azevedo K , Huard RC , Gallagher G , Hall J , Ash S , Kovar L , Seabolt MH , Weigand MR , Damon I , Satheshkumar PS , McCollum AM , Hutson CL , Wang X , Li Y . bioRxiv 2022 17 Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Identification of a Novel SARS-CoV-2 Delta-Omicron Recombinant Virus in the United States (preprint)
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Sakaguchi H , Peacock T , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Hassell N , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . bioRxiv 2022 21 Recombination between SARS-CoV-2 virus variants can result in different viral properties (e.g., infectiousness or pathogenicity). In this report, we describe viruses with recombinant genomes containing signature mutations from Delta and Omicron variants. These genomes are the first evidence for a Delta-Omicron hybrid Spike protein in the United States. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Selective whole genome amplification as a tool to enrich specimens with low Treponema pallidum genomic DNA copies for whole genome sequencing (preprint)
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . bioRxiv 2021 10 Downstream next generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome, and the capture and removal of CpG-methylated host DNA using the NEBNext Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14 T. pallidum genomic copies/ul of sample for SWGA and >129 genomic copies/ul for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which have been challenging until now. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021 (preprint)
Salvatore PP , Lee CC , Sleweon S , McCormick DW , Nicolae L , Knipe K , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Salmonson S , Ogden C , Godwin E , Ballom T , Ross T , Wynn NT , David E , Bessey TK , Kim G , Suppiah S , Tamin A , Harcourt JL , Sheth M , Lowe L , Browne H , Tate JE , Kirking HL , Hagan LM . medRxiv 2021 19 Background The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. Methods Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. Results A total of 978 specimens were provided by 95 participants, of whom 78 (82%) were fully vaccinated and 17 (18%) were not fully vaccinated. No significant differences were detected in duration of RT-PCR positivity among fully vaccinated participants (median: 13 days) versus those not fully vaccinated (median: 13 days; p=0.50), or in duration of culture positivity (medians: 5 days and 5 days; p=0.29). Among fully vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p=0.048) or Janssen (p=0.003) vaccine recipients. Conclusions As this field continues to develop, clinicians and public health practitioners should consider vaccinated persons who become infected with SARS-CoV-2 to be no less infectious than unvaccinated persons. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Genomic surveillance for SARS-CoV-2 variants: Circulation of Omicron lineages - United States, January 2022-May 2023
Ma KC , Shirk P , Lambrou AS , Hassell N , Zheng XY , Payne AB , Ali AR , Batra D , Caravas J , Chau R , Cook PW , Howard D , Kovacs NA , Lacek KA , Lee JS , MacCannell DR , Malapati L , Mathew S , Mittal N , Nagilla RR , Parikh R , Paul P , Rambo-Martin BL , Shepard SS , Sheth M , Wentworth DE , Winn A , Hall AJ , Silk BJ , Thornburg N , Kondor R , Scobie HM , Paden CR . MMWR Morb Mortal Wkly Rep 2023 72 (24) 651-656 ![]() CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics. |
Risk of Spontaneous Abortion After Inadvertent Human Papillomavirus Vaccination in Pregnancy
Kharbanda EO , Vazquez-Benitez G , Lipkind HS , Sheth SS , Zhu J , Naleway AL , Klein NP , Hechter R , Daley MF , Donahue JG , Jackson ML , Kawai AT , Sukumaran L , Nordin JD . Obstet Gynecol 2018 132 (1) 35-44 OBJECTIVE: To evaluate the risk of spontaneous abortion after quadrivalent human papillomavirus (4vHPV) vaccination before and during pregnancy across seven integrated health systems within the Vaccine Safety Datalink. METHODS: Within a retrospective observational cohort, we compared risks for spontaneous abortion after 4vHPV in three exposure windows: distal (16-22 weeks before the last menstrual period [LMP]), peripregnancy (within 6 weeks before the LMP), and during pregnancy (LMP through 19 weeks of gestation). Women 12-27 years of age with a pregnancy between 2008 and 2014, with continuous insurance enrollment 8 months before and through pregnancy end, and with a live birth, stillbirth, or spontaneous abortion were included. Pregnancies were identified through validated algorithms. Spontaneous abortions and stillbirths were verified by chart review with spontaneous abortions adjudicated by clinical experts. We excluded multiple gestations, spontaneous abortions before 6 weeks of gestation, and women using medications increasing risk of spontaneous abortion. Spontaneous abortion risk after 4vHPV during pregnancy was compared with distal vaccination using time-dependent covariate Cox models. Spontaneous abortion risk for peripregnancy compared with distal vaccination was evaluated with standard Cox models. RESULTS: We identified 2,800 pregnancies with 4vHPV exposure in specified risk windows: 919 (33%) distal, 986 (35%) peripregnancy, and 895 (32%) during pregnancy. Mean age was 22.4 years in distal and peripregnancy groups compared with 21.4 years among women vaccinated during pregnancy. Among women with distal 4vHPV exposure, 96 (10.4%) experienced a spontaneous abortion. For peripregnancy and during pregnancy exposures, spontaneous abortions occurred in 110 (11.2%) and 77 (8.6%), respectively. The risk of spontaneous abortion was not increased among women who received 4vHPV during pregnancy (adjusted hazard ratio 1.10, 95% CI 0.81-1.51) or peripregnancy 1.07 (0.81-1.41). CONCLUSION: Inadvertent 4vHPV exposure during or peripregnancy was not significantly associated with an increased risk of spontaneous abortion. |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021.
Salvatore PP , Lee CC , Sleweon S , McCormick DW , Nicolae L , Knipe K , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Salmonson S , Ogden C , Godwin E , Ballom T , Rhodes T , Wynn NT , David E , Bessey TK , Kim G , Suppiah S , Tamin A , Harcourt JL , Sheth M , Lowe L , Browne H , Tate JE , Kirking HL , Hagan LM . Vaccine 2022 41 (11) 1808-1818 ![]() ![]() BACKGROUND: The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. METHODS: Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. RESULTS: A total of 957 specimens were provided by 93 participants, of whom 78 (84 %) were vaccinated and 17 (16 %) were unvaccinated. No significant differences were detected in duration of RT-PCR positivity among vaccinated participants (median: 13 days) versus those unvaccinated (median: 13 days; p = 0.50), or in duration of culture positivity (medians: 5 days and 5 days; p = 0.29). Among vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p = 0.048) or Janssen (p = 0.003) vaccine recipients. In post-hoc analyses, Moderna vaccine recipients demonstrated significantly shorter duration of culture positivity compared to unvaccinated participants (p = 0.02). When restricted to participants without reported prior infection, the difference between Moderna vaccine recipients and unvaccinated participants was more pronounced (medians: 3 days and 6 days, p = 0.002). CONCLUSIONS: Infectious periods for vaccinated and unvaccinated persons who become infected with SARS-CoV-2 are similar and can be highly variable, though some vaccinated persons are likely infectious for shorter durations. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. In such settings, clinicians and public health practitioners should consider vaccinated, infected persons to be no less infectious than unvaccinated, infected persons. |
SARS-CoV-2 viral shedding in vaccinated and unvaccinated persons: A case series.
McCormick DW , Hagan LM , Salvatore PP , Magleby R , Lee C , Sleweon S , Nicolae L , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Ogden C , Browne H , Michael Metz J , Chen MH , Solano MI , Rogers S , Burgin A , Sheth M , Bankamp B , Tamin A , Harcourt JL , Tate JE , Kirking HL . Vaccine 2022 41 (11) 1769-1773 The preclinical time course of SARS-CoV-2 shedding is not well-described. Understanding this time course will help to inform risk of SARS-CoV-2 transmission. During an outbreak in a congregate setting, we collected paired mid-turbinate nasal swabs for antigen testing and reverse-transcription polymerase chain reaction (RT-PCR) every other day from all consenting infected and exposed persons. Among 12 persons tested prospectively before and during SARS-CoV-2 infection, ten of 12 participants (83%) had completed a primary COVID-19 vaccination series prior to the outbreak. We recovered SARS-CoV-2 in viral culture from 9/12 (75%) of participants. All three persons from whom we did not recover SARS-CoV-2 in viral culture had completed their primary vaccination series. We recovered SARS-CoV-2 from viral culture in 6/9 vaccinated persons and before symptom onset in 3/6 symptomatic persons. These findings underscore the need for both non-pharmaceutical interventions and vaccination to mitigate transmission. |
The first complete genome of the simian malaria parasite Plasmodium brasilianum.
Bajic M , Ravishankar S , Sheth M , Rowe LA , Pacheco MA , Patel DS , Batra D , Loparev V , Olsen C , Escalante AA , Vannberg F , Udhayakumar V , Barnwell JW , Talundzic E . Sci Rep 2022 12 (1) 19802 ![]() ![]() Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has been available. Previously, we reported a draft genome for P. brasilianum, and here we report the completed genome for P. brasilianum. The genome is 31.4 Mb in size and comprises 14 chromosomes, the mitochondrial genome, the apicoplast genome, and 29 unplaced contigs. The chromosomes consist of 98.4% nucleotide sites that are identical to the P. malariae genome, the closest evolutionarily related species hypothesized to be the same species as P. brasilianum, with 41,125 non-synonymous SNPs (0.0722% of genome) identified between the two genomes. Furthermore, P. brasilianum had 4864 (82.1%) genes that share 80% or higher sequence similarity with 4970 (75.5%) P. malariae genes. This was demonstrated by the nearly identical genomic organization and multiple sequence alignments for the merozoite surface proteins msp3 and msp7. We observed a distinction in the repeat lengths of the circumsporozoite protein (CSP) gene sequences between P. brasilianum and P. malariae. Our results demonstrate a 97.3% pairwise identity between the P. brasilianum and the P. malariae genomes. These findings highlight the phylogenetic proximity of these two species, suggesting that P. malariae and P. brasilianum are strains of the same species, but this could not be fully evaluated with only a single genomic sequence for each species. |
SARS-CoV-2 Delta-Omicron Recombinant Viruses, United States.
Lacek KA , Rambo-Martin BL , Batra D , Zheng XY , Hassell N , Sakaguchi H , Peacock T , Groves N , Keller M , Wilson MM , Sheth M , Davis ML , Borroughs M , Gerhart J , Shepard SS , Cook PW , Lee J , Wentworth DE , Barnes JR , Kondor R , Paden CR . Emerg Infect Dis 2022 28 (7) 1442-1445 ![]() ![]() To detect new and changing SARS-CoV-2 variants, we investigated candidate Delta-Omicron recombinant genomes from Centers for Disease Control and Prevention national genomic surveillance. Laboratory and bioinformatic investigations identified and validated 9 genetically related SARS-CoV-2 viruses with a hybrid Delta-Omicron spike protein. |
Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Kiniry E , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Moehling Geffel K , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M . Influenza Other Respir Viruses 2022 16 (6) 975-985 Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Mann BR , Hossain J , Lin X , Lester S , Pusch EA , Jones J , Cui D , Chatterjee P , Jenks MH , Morantz EK , Larson GP , Hatta M , Harcourt JL , Tamin A , Li Y , Tao Y , Zhao K , Lacek K , Burroughs A , Wang W , Wilson M , Wong T , Park SH , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Halpin AL , McMullan LK , Lee JS , Xia H , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan VG , Wentworth DE , Zhou B . Nat Commun 2022 13 (1) 4350 ![]() ![]() The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic. |
Selective Whole-Genome Amplification as a Tool to Enrich Specimens with Low Treponema pallidum Genomic DNA Copies for Whole-Genome Sequencing.
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . mSphere 2022 7 (3) e0000922 ![]() ![]() Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome and the capture and removal of 5'-C-phosphate-G-3' (CpG) methylated host DNA using the NEBNext Microbiome DNA enrichment kit followed by MDA with the REPLI-g single cell kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93 to 98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit-propagated isolates, containing >14 T. pallidum genomic copies/μL of sample for SWGA and >129 genomic copies/μL for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole-genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which has been challenging until now. IMPORTANCE Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogen Treponema pallidum subspecies pallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions and, if left untreated, can progress through multiple stages with various clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past 2 decades, WGS data are needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of an SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers of T. pallidum. |
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