Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-30 (of 206 Records) |
Query Trace: Lawrence M[original query] |
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The roles of habitat isolation, landscape connectivity and host community in tick-borne pathogen ecology
Shaw G , Lilly M , Mai V , Clark J , Summers S , Slater K , Karpathy S , Nakano A , Crews A , Lawrence A , Salomon J , Sambado SB , Swei A . R Soc Open Sci 2024 11 (11) 240837 Habitat loss and forest fragmentation are often linked to increased pathogen transmission, but the extent to which habitat isolation and landscape connectivity affect disease dynamics through movement of disease vectors and reservoir hosts has not been well examined. Tick-borne diseases are the most prevalent vector-borne diseases in the United States and on the West Coast, Ixodes pacificus is one of the most epidemiologically important vectors. We investigated the impacts of habitat fragmentation on pathogens transmitted by I. pacificus and sought to disentangle the effects of wildlife communities and landscape metrics predictive of pathogen diversity, prevalence and distribution. We collected pathogen data for four co-occurring bacteria transmitted by I. pacificus and measured wildlife parameters. We also used spatial data and cost-distance analysis integrating expert opinions to assess landscape metrics of habitat fragmentation. We found that landscape metrics were significant predictors of tick density and pathogen prevalence. However, wildlife variables were essential when predicting the prevalence and distribution of pathogens reliant on wildlife reservoir hosts for maintenance. We found that landscape structure was an informative predictor of tick-borne pathogen richness in an urban matrix. Our work highlights the implications of large-scale land management on human disease risk. |
Varicella outbreak among recent arrivals to New York City, 2022-2024
Graham KA , Arciuolo RJ , Matalka O , Isaac BM , Jean A , Majid N , Seifu L , Croft J , Crouch B , Macaraig M , Lemkin A , Caceres GT , Lall R , Lawrence C , Silverman E , Laraque F , Bouscaren A , Rosen JB . MMWR Morb Mortal Wkly Rep 2024 73 (21) 478-483 |
Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases.
Arias A , Watson SJ , Asogun D , Tobin EA , Lu J , Phan MVT , Jah U , Wadoum REG , Meredith L , Thorne L , Caddy S , Tarawalie A , Langat P , Dudas G , Faria NR , Dellicour S , Kamara A , Kargbo B , Kamara BO , Gevao S , Cooper D , Newport M , Horby P , Dunning J , Sahr F , Brooks T , Simpson AJH , Groppelli E , Liu G , Mulakken N , Rhodes K , Akpablie J , Yoti Z , Lamunu M , Vitto E , Otim P , Owilli C , Boateng I , Okoror L , Omomoh E , Oyakhilome J , Omiunu R , Yemisis I , Adomeh D , Ehikhiametalor S , Akhilomen P , Aire C , Kurth A , Cook N , Baumann J , Gabriel M , Wölfel R , Di Caro A , Carroll MW , Günther S , Redd J , Naidoo D , Pybus OG , Rambaut A , Kellam P , Goodfellow I , Cotten M . Virus Evol 2016 2 (1) vew016 To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts. |
The distribution of triatomine (Hemiptera: Reduviidae) vectors of Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) in Illinois and Missouri: historical records and specimen submissions from community science programs
Santos EM , Santanello CD , Curtis-Robles R , Killets K , Lawrence G , Sevenshadows J , Mahoney MJ , Baker M , Hamer SA . J Med Entomol 2023 Triatomine species (kissing bugs) infected with Trypanosoma cruzi are found across the southern United States. The northern limits of Trypanosoma cruzi infected kissing bugs are less understood. The objective of this work was to describe the locations of kissing bugs from Illinois and Missouri based on historical records, submissions to Texas A&M University's (TAMU) Kissing Bug Community Science Program and the Centers for Disease Control and Prevention (CDC), and records from online platforms (iNaturalist, BugGuide, and GBIF) up to and including 2022. A total of 228 records were discovered, including 186 from historical or observation platforms and 42 specimens submitted to TAMU or CDC. Species included Triatoma sanguisuga (221 total records, 9 nymphs) and Triatoma lecticularia (7 records). Notably, nearly all (24/26) records submitted to TAMU were collected indoors. Twelve of the 30 (40%) specimens tested were positive for the presence of T. cruzi, including parasite discrete taxonomic units TcI and TcIV. One triatomine sample had been found in a bed feeding on the submitter; this bug was positive for T. cruzi and had evidence of human blood in its gut. Records suggest a ubiquitous distribution in Missouri and potentially to the northernmost border in Illinois. Further investigations into triatomine distribution and infection status are needed within states assumed to be northern limits in order to create public health and veterinary health messaging and baseline distributional maps from which to measure future range shifts in relation to a changing climate. |
Genomic characterization of cocirculating Corynebacterium diphtheriae and non-diphtheritic Corynebacterium species among forcibly displaced Myanmar nationals, 2017-2019
Xiaoli L , Peng Y , Williams MM , Lawrence M , Cassiday PK , Aneke JS , Pawloski LC , Shil SR , Rashid MO , Bhowmik P , Weil LM , Acosta AM , Shirin T , Habib ZH , Tondella ML , Weigand MR . Microb Genom 2023 9 (9) Respiratory diphtheria is a serious infection caused by toxigenic Corynebacterium diphtheriae, and disease transmission mainly occurs through respiratory droplets. Between 2017 and 2019, a large diphtheria outbreak among forcibly displaced Myanmar nationals densely settled in Bangladesh was investigated. Here we utilized whole-genome sequencing (WGS) to characterize recovered isolates of C. diphtheriae and two co-circulating non-diphtheritic Corynebacterium (NDC) species - C. pseudodiphtheriticum and C. propinquum. C. diphtheriae isolates recovered from all 53 positive cases in this study were identified as toxigenic biovar mitis, exhibiting intermediate resistance to penicillin, and formed four phylogenetic clusters circulating among multiple refugee camps. Additional sequenced isolates collected from two patients showed co-colonization with non-toxigenic C. diphtheriae biovar gravis, one of which exhibited decreased susceptibility to the first-line antibiotics and harboured a novel 23-kb multidrug resistance plasmid. Results of phylogenetic reconstruction and virulence-related gene contents of the recovered NDC isolates indicated they were likely commensal organisms, though 80.4 %(45/56) were not susceptible to erythromycin, and most showed high minimum inhibition concentrations against azithromycin. These results demonstrate the high resolution with which WGS can aid molecular investigation of diphtheria outbreaks, through the quantification of bacterial genetic relatedness, as well as the detection of virulence factors and antibiotic resistance markers among case isolates. |
Gene flux and acid-imposed selection are the main drivers of antimicrobial resistance in broiler chicks infected with Salmonella enterica serovar Heidelberg (preprint)
Oladeinde A , Abdo Z , Press MO , Cook K , Cox NA , Zwirzitz B , Woyda R , Lakin SM , Thomas JCIV , Looft T , Cosby DE , Hinton AJr , Guard J , Line E , Rothrock MJ , Berrang ME , Herrington K , Zock G , Plumblee Lawrence J , Cudnik D , House S , Ingram K , Lariscy L , Wagner M , Aggrey SE , Chai L , Ritz C . bioRxiv 2021 2021.02.25.432983 Antimicrobial resistance (AR) spread is a worldwide health challenge, stemming in large part, from the ability of microbes to share their genetic material through horizontal gene transfer (HGT). Overuse and misuse of antibiotics in clinical settings and in food production have been linked to this increased prevalence and spread of AR. Consequently, public health and consumer concerns have resulted in a remarkable recent reduction in antibiotics used for food animal production. This is driven by the assumption that removing this selective pressure will favor the recovery of antibiotic susceptible taxa and will limit AR sharing through HGT, allowing the currently available antibiotic arsenal to be effective for a longer period. In this study we used broiler chicks raised antibiotic-free and Salmonella enterica serovar Heidelberg (SH), as a model food pathogen, to test this hypothesis. Our results show that neonatal broiler chicks challenged with an antibiotic susceptible SH strain and raised without antibiotics carried susceptible and multidrug resistance SH strains 14 days after challenge. SH infection perturbed the microbiota of broiler chicks and gavaged chicks acquired antibiotic resistant SH at a higher rate. We determined that the acquisition of a plasmid from commensal Escherichia coli population conferred multidrug resistance phenotype to SH recipients and carriage of this plasmid increased the fitness of SH under acidic selection pressure. These results suggest that HGT of AR shaped the evolution of SH and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella.Importance The reported increase in antibiotic resistant bacteria in humans have resulted in a major shift away from antibiotics use in food animal production. This has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, and this in turn will allow the currently available antibiotic arsenal to be more effective. This shift in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic susceptible Salmonella Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggests that simply removing antibiotics from food-animal production might not be sufficient to limit the spread of antimicrobial resistance.Competing Interest StatementThe authors have declared no competing interest. |
Competition is a determinant of multidrug resistant plasmid acquisition in Salmonella (preprint)
Oladeinde A , Abdo Z , Zwirzitz B , Woyda R , Lakin SM , Press MO , Cook K , Cox NA , Thomas JCIV , Looft T , Rothrock MJJr , Zock G , Plumblee Lawrence J , Cudnik D , Ritz C , Aggrey SE . bioRxiv 2021 2021.04.02.438293 Host microbiome homeostasis ensures that gut conditions are unfavorable to an invading pathogen such as Salmonella enterica. Consequently, fostering a “balanced” gut microbiome through the administration of microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known on how competitive exclusion affects the transfer of antibiotic resistance. To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter – a complex environment comprising of decomposing pine shavings, feces, uric acid, feathers, and feed, with Salmonella Heidelberg (S. Heidelberg), a model pathogen. We show that chicks raised on reused litter carried lower abundance of Salmonella and harbored a more uniform and diverse microbiome comprising of bacterial species that are known to provide colonization resistance towards Salmonella compared to chicks raised on fresh bedding composed of pine shavings. Additionally, these bacterial species were associated with a lower horizontal transfer of multidrug resistance genes to S. Heidelberg. Using in vitro competition experiments, we confirmed that conjugation between S. Heidelberg and E. coli strains from chicks raised on fresh litter resulted in the acquisition of multidrug resistant plasmids. Contrastingly, bacteriophage-mediated recombination between S. Heidelberg and E. coli strains made the acquisition of plasmid-mediated β-lactamase gene (blaCMY-2) possible. Collectively, this study demonstrates that competitive exclusion can reduce the transfer of antibiotic resistance and provides information on the bacterial species that can be explored for their benefits to reduce antibiotic resistance transfer.Importance/Significance Antimicrobial resistance spread is a worldwide health challenge, stemming in large part, from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organization have adopted a one health approach to curtail the proliferation of antibiotic resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how antimicrobial resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we demonstrate that commensal bacteria play a key role in reducing the horizontal transfer of antibiotic resistance to Salmonella and provide the identity and characteristics of the bacterial species that performs this function in broiler chickens. |
Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa (preprint)
Jeffries CL , Lawrence GG , Golovko G , Kristan M , Orsborne J , Spence K , Hurn E , Bandibabone J , Tantely LM , Raharimalala FN , Keita K , Camara D , Barry Y , Wat'senga F , Manzambi EZ , Afrane YA , Mohammed AR , Abeku TA , Hedge S , Khanipov K , Pimenova M , Fofanov Y , Boyer S , Irish SR , Hughes GL , Walker T . bioRxiv 2018 338434 Anopheles (An.) mosquitoes contain bacteria that can influence Plasmodium parasites. Wolbachia, a common insect endosymbiont, has historically been considered absent from Anopheles but has recently been found in An. gambiae populations. Here, we assessed a range of Anopheles species from five malaria-endemic countries for Wolbachia and Plasmodium infection. Strikingly, we found Wolbachia infections in An. coluzzii, An. gambiae s.s, An. arabiensis, An. moucheti and An. species ‘A’ increasing the number of Anopheles species known to be naturally infected by this endosymbiont. Molecular analysis suggests the presence of phylogenetically diverse novel strains, while qPCR and 16S rRNA sequencing indicates that Wolbachia is the dominant member of the microbiota in An. moucheti and An. species ‘A’. We found no evidence of Wolbachia/Asaia co-infections, and presence of these endosymbionts did not have significant effects on malaria prevalence. We discuss the importance of novel Wolbachia strains in Anopheles and potential implications for disease control. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Notes from the Field: Legionnaires disease in a U.S. traveler after staying in a private vacation rental house in the U.S. Virgin Islands - United States, February 2022
Mac VV , Labgold K , Moline HL , Smith JC , Carroll J , Clemmons N , Edens C , Ellis B , Harrison C , Henderson KC , Ishaq MK , Kozak-Muiznieks NA , Kunz J , Lawrence M , Lucas CE , Walker HL , Willby MJ , Ellis EM . MMWR Morb Mortal Wkly Rep 2023 72 (20) 564-565 On February 1, 2022, the U.S. Virgin Islands (USVI) Department of Health (VIDOH) was notified of a confirmed case of Legionnaires disease in an adult U.S. resident (Figure). The patient, a man aged 55 years, returned to his U.S. state of residence from leisure travel in USVI on January 22 and developed a cough, shortness of breath, and fatigue on January 23. On January 29, he was hospitalized for shortness of breath and received a positive SARS-CoV-2 test result at admission. The combination of the patient’s symptoms and recent travel history prompted administration of a urinary antigen test (UAT) for Legionnaires disease specific to Legionella pneumophila serogroup 1 (Lp1); a positive result was returned on January 31. Inpatient treatment administered for COVID-19 pneumonia and Legionnaires disease included remdesivir, oral levofloxacin, oral and intravenous steroid therapy, and as-needed use of a bronchodilator inhaler and an expectorant. Remdesivir was discontinued during inpatient treatment because of elevated liver enzymes. The patient recovered and was discharged on February 2. |
Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study
Pneumonia Etiology Research for Child Health Study Group , O'Brien Katherine L , Levine Orin S , Knoll Maria Deloria , Feikin Daniel R , DeLuca Andrea N , Driscoll Amanda J , Fancourt Nicholas , Fu Wei , Haddix Meredith , Hammitt Laura L , Higdon Melissa M , Kagucia E Wangeci , Karron Ruth A , Li Mengying , Park Daniel E , Prosperi Christine , Shi Qiyuan , Wu Zhenke , Zeger Scott L , Watson Nora L , Crawley Jane , Murdoch David R , Brooks W Abdullah , Endtz Hubert P , Zaman Khalequ , Goswami Doli , Hossain Lokman , Jahan Yasmin , Chisti Mohammod Jobayer , Howie Stephen R C , Ebruke Bernard E , Antonio Martin , McLellan Jessica L , Machuka Eunice M , Shamsul Arifin , Zaman Syed M A , Mackenzie Grant , Scott J Anthony G , Awori Juliet O , Morpeth Susan C , Kamau Alice , Kazungu Sidi , Ominde Micah Silaba , Kotloff Karen L , Tapia Milagritos D , Sow Samba O , Sylla Mamadou , Tamboura Boubou , Onwuchekwa Uma , Kourouma Nana , Toure Aliou , Sissoko Seydou , Madhi Shabir A , Moore David P , Adrian Peter V , Baillie Vicky L , Kuwanda Locadiah , Mudau Azwifarwi , Groome Michelle J , Mahomed Nasreen , Simões Eric A F , Baggett Henry C , Thamthitiwat Somsak , Maloney Susan A , Bunthi Charatdao , Rhodes Julia , Sawatwong Pongpun , Akarasewi Pasakorn , Thea Donald M , Mwananyanda Lawrence , Chipeta James , Seidenberg Phil , Mwansa James , Somwe Somwe Wa , Kwenda Geoffrey , Anderson Trevor P , Mitchell Joanne L . Lancet 2019 394 (10200) 757-779 BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation. |
Adapterama II: universal amplicon sequencing on Illumina platforms (TaggiMatrix).
Glenn TC , Pierson TW , Bayona-Vásquez NJ , Kieran TJ , Hoffberg SL , Thomas Iv JC , Lefever DE , Finger JW , Gao B , Bian X , Louha S , Kolli RT , Bentley KE , Rushmore J , Wong K , Shaw TI , Rothrock MJ Jr , McKee AM , Guo TL , Mauricio R , Molina M , Cummings BS , Lash LH , Lu K , Gilbert GS , Hubbell SP , Faircloth BC . PeerJ 2019 7 e7786 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. In many cases, NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5' end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (8 forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy. |
Correction: A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health.
Khoury MJ , Feero WG , Chambers DA , Brody LC , Aziz N , Green RC , Janssens Acjw , Murray MF , Rodriguez LL , Rutter JL , Schully SD , Winn DM , Mensah GA . PLoS Med 2018 15 (8) e1002650 The fourth author’s name is incorrect. The correct name is Lawrence C. Brody. The correct citation is: Khoury MJ, Feero WG, Chambers DA, Brody LC, Aziz N, Green RC, et al. (2018) A collaborative translational research framework for evaluating and implementing the appropriate use of human genome sequencing to improve health. PLoS Med 15(8): e1002631. https://doi.org/10.1371/journal.pmed.1002631. |
Prevalence, progression, and modifiable risk factors for diabetic retinopathy in youth and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes In Youth Study
Jensen ET , Rigdon J , Rezaei KA , Saaddine J , Lundeen EA , Dabelea D , Dolan LM , D'Agostino R , Klein B , Meuer S , Mefford MT , Reynolds K , Marcovina SM , Mottl A , Mayer-Davis B , Lawrence JM . Diabetes Care 2023 46 (6) 1252-1260 OBJECTIVE: To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes. RESEARCH DESIGN AND METHODS: We conducted a multicenter, population-based prospective cohort study (2002-2019) of youth and young adults with youth-onset type 1 diabetes (n = 2,519) and type 2 diabetes (n = 447). Modifiable factors included baseline and change from baseline to follow-up in BMI z score, waist/height ratio, systolic and diastolic blood pressure z score, and A1C. DR included evidence of mild or moderate nonproliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR, and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up. RESULTS: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (mean [SD] 12.5 [2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with the observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted. CONCLUSIONS: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ∼12 years postdiagnosis. Tight glucose and blood pressure management may offer the opportunity to mitigate development and progression of DR in youth-onset diabetes. |
Notes from the field: Prevalence of previous dengue virus infection among children and adolescents - U.S. Virgin Islands, 2022
Mac VV , Wong JM , Volkman HR , Perez-Padilla J , Wakeman B , Delorey M , Biggerstaff BJ , Fagre A , Gumbs A , Drummond A , Zimmerman B , Lettsome B , Medina FA , Paz-Bailey G , Lawrence M , Ellis B , Rosenblum HG , Carroll J , Roth J , Rossington J , Meeker JR , Joseph J , Janssen J , Ekpo LL , Carrillo M , Hernandez N , Charles P , Tosado R , Soto R , Battle S , Bart SM , Wanga V , Valentin W , Powell W , Battiste Z , Ellis EM , Adams LE . MMWR Morb Mortal Wkly Rep 2023 72 (11) 288-289 In May 2019, the Food and Drug Administration issued approval for Dengvaxia (Sanofi Pasteur), a live-attenuated, chimeric tetravalent dengue vaccine (1). In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended vaccination with Dengvaxia for children and adolescents aged 9–16 years with laboratory confirmation of previous dengue virus infection and who live in areas with endemic dengue transmission, such as the U.S. Virgin Islands (USVI)† (2). Confirming previous dengue virus infection before vaccine administration (prevaccination screening) is important because 1) although Dengvaxia decreases hospitalization and severe disease from dengue among persons with a previous infection, it increases the risk for these outcomes among persons without a previous infection; 2) many dengue virus infections are asymptomatic; and 3) many patients with symptomatic infections do not seek medical attention or receive appropriate testing (3). Sufficient laboratory evidence of previous dengue virus infection includes a history of laboratory-confirmed dengue§ or a positive serologic test result that meets ACIP-recommended performance standards for prevaccination screening, defined as high specificity (≥98%) and sensitivity (≥75%). A seroprevalence of 20% in the vaccine-eligible population (corresponding to a positive predictive value of ≥90% for a test with minimum sensitivity of 75% and minimum specificity of 98%) is recommended to maximize vaccine safety and minimize the risk for vaccinating persons without a previous dengue virus infection (2). |
Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002-18: results from the population-based SEARCH for Diabetes in Youth study
Wagenknecht LE , Lawrence JM , Isom S , Jensen ET , Dabelea D , Liese AD , Dolan LM , Shah AS , Bellatorre A , Sauder K , Marcovina S , Reynolds K , Pihoker C , Imperatore G , Divers J . Lancet Diabetes Endocrinol 2023 11 (4) 242-250 BACKGROUND: The incidence of diabetes is increasing in children and young people. We aimed to describe the incidence of type 1 and type 2 diabetes in children and young people aged younger than 20 years over a 17-year period. METHODS: The SEARCH for Diabetes in Youth study identified children and young people aged 0-19 years with a physician diagnosis of type 1 or type 2 diabetes at five centres in the USA between 2002 and 2018. Eligible participants included non-military and non-institutionalised individuals who resided in one of the study areas at the time of diagnosis. The number of children and young people at risk of diabetes was obtained from the census or health plan member counts. Generalised autoregressive moving average models were used to examine trends, and data are presented as incidence of type 1 diabetes per 100 000 children and young people younger than 20 years and incidence of type 2 diabetes per 100 000 children and young people aged between 10 years and younger than 20 years across categories of age, sex, race or ethnicity, geographical region, and month or season of diagnosis. FINDINGS: We identified 18 169 children and young people aged 0-19 years with type 1 diabetes in 85 million person-years and 5293 children and young people aged 10-19 years with type 2 diabetes in 44 million person-years. In 2017-18, the annual incidence of type 1 diabetes was 22·2 per 100 000 and that of type 2 diabetes was 17·9 per 100 000. The model for trend captured both a linear effect and a moving-average effect, with a significant increasing (annual) linear effect for both type 1 diabetes (2·02% [95% CI 1·54-2·49]) and type 2 diabetes (5·31% [4·46-6·17]). Children and young people from racial and ethnic minority groups such as non-Hispanic Black and Hispanic children and young people had greater increases in incidence for both types of diabetes. Peak age at diagnosis was 10 years (95% CI 8-11) for type 1 diabetes and 16 years (16-17) for type 2 diabetes. Season was significant for type 1 diabetes (p=0·0062) and type 2 diabetes (p=0·0006), with a January peak in diagnoses of type 1 diabetes and an August peak in diagnoses of type 2 diabetes. INTERPRETATION: The increasing incidence of type 1 and type 2 diabetes in children and young people in the USA will result in an expanding population of young adults at risk of developing early complications of diabetes whose health-care needs will exceed those of their peers. Findings regarding age and season of diagnosis will inform focused prevention efforts. FUNDING: US Centers for Disease Control and Prevention and US National Institutes of Health. |
Estimating incidence of type 1 and type 2 diabetes using prevalence data: the SEARCH for Diabetes in Youth study
Hoyer A , Brinks R , Tönnies T , Saydah SH , D'Agostino RB Jr , Divers J , Isom S , Dabelea D , Lawrence JM , Mayer-Davis EJ , Pihoker C , Dolan L , Imperatore G . BMC Med Res Methodol 2023 23 (1) 39 BACKGROUND: Incidence is one of the most important epidemiologic indices in surveillance. However, determining incidence is complex and requires time-consuming cohort studies or registries with date of diagnosis. Estimating incidence from prevalence using mathematical relationships may facilitate surveillance efforts. The aim of this study was to examine whether a partial differential equation (PDE) can be used to estimate diabetes incidence from prevalence in youth. METHODS: We used age-, sex-, and race/ethnicity-specific estimates of prevalence in 2001 and 2009 as reported in the SEARCH for Diabetes in Youth study. Using these data, a PDE was applied to estimate the average incidence rates of type 1 and type 2 diabetes for the period between 2001 and 2009. Estimates were compared to annual incidence rates observed in SEARCH. Precision of the estimates was evaluated using 95% bootstrap confidence intervals. RESULTS: Despite the long period between prevalence measures, the estimated average incidence rates mirror the average of the observed annual incidence rates. Absolute values of the age-standardized sex- and type-specific mean relative errors are below 8%. CONCLUSIONS: Incidence of diabetes can be accurately estimated from prevalence. Since only cross-sectional prevalence data is required, employing this methodology in future studies may result in considerable cost savings. |
Effects of COVID-19 pandemic on voluntary medical male circumcision services for HIV prevention, Sub-Saharan Africa, 2020
Peck ME , Ong KS , Lucas T , Prainito A , Thomas AG , Brun A , Kiggundu V , Yansaneh A , Busang L , Kgongwana K , Kelaphile D , Seipone K , Letebele MH , Makadzange PF , Marwiro A , Sesinyi M , Lapidos T , Lukhele N , Maziya V , Mkhontfo M , Gultie T , Mulatu D , Shimelis M , Zegeye T , Teka T , Bulterys M , Njenga JN , Odoyo-June E , Juma AW , Soo L , Talam N , Brown M , Chakare T , Nonyana N , Khoabane MA , Auld AF , Maida A , Msungama W , Kapito M , Nyirenda R , Matchere F , Odek J , Canda M , Malimane I , Come J , Gaspar N , Langa A , Aupokolo MA , Vejorerako KC , Kahindi L , Mali D , Zegeye A , Mangoya D , Zemburuka BL , Bamwesigye J , Kankindi I , Kayirangwa E , Malamba SS , Roels T , Kayonde L , Zimulinda E , Ndengo E , Nsanzimana S , Remera E , Rwibasira GN , Sangwayire B , Semakula M , Rugira E , Rugwizangoga E , Tubane E , Yoboka E , Lawrence J , Loykissoonlal D , Maphothi N , Achut V , Bunga S , Moi M , Amuri M , Kazaura K , Simbeye D , Fida N , Kayange AA , Seleman M , Akao J , Alamo ST , Kabuye G , Kyobutungi S , Makumbi FE , Mudiope P , Nantez B , Chituwo O , Godfrey L , Muyunda B , Kamboyi R , Masiye J , Lifuka E , Mandisarisa J , Mhangara M , Xaba S , Toledo C . Emerg Infect Dis 2022 28 (13) S262-s269 Beginning in March 2020, to reduce COVID-19 transmission, the US President's Emergency Plan for AIDS Relief supporting voluntary medical male circumcision (VMMC) services was delayed in 15 sub-Saharan African countries. We reviewed performance indicators to compare the number of VMMCs performed in 2020 with those performed in previous years. In all countries, the annual number of VMMCs performed decreased 32.5% (from 3,898,960 in 2019 to 2,631,951 in 2020). That reduction is largely attributed to national and local COVID-19 mitigation measures instituted by ministries of health. Overall, 66.7% of the VMMC global annual target was met in 2020, compared with 102.0% in 2019. Countries were not uniformly affected; South Africa achieved only 30.7% of its annual target in 2020, but Rwanda achieved 123.0%. Continued disruption to the VMMC program may lead to reduced circumcision coverage and potentially increased HIV-susceptible populations. Strategies for modifying VMMC services provide lessons for adapting healthcare systems during a global pandemic. |
Racial disparities in severe maternal morbidity in an integrated health care system, Southern California, 2008-2017
Oakley LP , Li X , Tartof SY , Wilkes-Grundy M , Fassett MJ , Lawrence JM . Womens Health Issues 2023 33 (3) 280-288 OBJECTIVE: The study's objectives were to examine rates of severe maternal morbidity (SMM) over a 10-year period and assess racial/ethnic disparities in SMM among insured women in a large, integrated health care system in Southern California. METHODS: We included Kaiser Permanente Southern California (KPSC) health plan members who gave birth at ≥20 weeks' gestation in a KPSC-owned hospital during 2008-2017. An SMM case was defined as presence of one or more indicators of an SMM event during a birth hospitalization, identified using maternal electronic health records. Crude SMM rates/10,000 births were calculated by year and maternal race/ethnicity. Modified Poisson regression models were used to assess the association between race/ethnicity and SMM adjusted for other maternal demographics, pregnancy characteristics, and preexisting conditions. RESULTS: We identified 5,915 SMM cases among 335,310 births. Crude SMM rates increased from 94.7 per 10,000 in 2008 to 192.6 in 2015 and 249.5 in 2017. Non-Hispanic Black (adjusted risk ratio [aRR] 1.52; 95% confidence interval [CI] 1.37-1.69), Asian/Pacific Islander (aRR 1.29, 95% CI 1.18-1.41), and Hispanic (aRR 1.18, 95% CI 1.10-1.27) women had greater likelihood of SMM than non-Hispanic White women. After further adjusting for preexisting health conditions, differences in SMM by race/ethnicity remained. CONCLUSIONS: SMM rates increased during 2008-2017 and women of racial and ethnic minority groups, particularly non-Hispanic Black women, were more likely to experience an SMM event than non-Hispanic White women. Multilevel approaches to understanding structural and social factors that may be associated with racial and ethnic disparities in SMM are needed to develop and test effective interventions to reduce SMM. |
Support for policies to prohibit the sale of menthol cigarettes and all tobacco products among adults, 2021
Al-Shawaf M , Grooms KN , Mahoney M , Buchanan Lunsford N , Lawrence Kittner D . Prev Chronic Dis 2023 20 E05 This study assessed support for commercial tobacco retail policies among adults. Data came from SpringStyles 2021, a web panel survey of adults in the US aged 18 years or older (N = 6,455). Overall, 62.3% of adults supported a policy prohibiting the sale of menthol cigarettes, and 57.3% supported a policy prohibiting the sale of all tobacco products. A majority of adults supported tobacco retail policies aimed at preventing initiation, promoting quitting, and reducing tobacco-related disparities. These findings can help inform federal, state, and local efforts to prohibit the sale of tobacco products, including menthol cigarettes. |
Strategies to reduce harm: An expert panel discussion on the fentanyl crisis
Leitz SJ , Bagley SM , Cook AJ , Jones C , Lawrence D , Pearce P . Perm J 2023 27 (1) 1-13 According to provisional data from the Centers for Disease Control and Prevention (CDC), during the 12-month period ending in July 2022, an estimated 107,500 1 lives were lost to a drug overdose. More than 81,000 of the overdose deaths involved opioids. These numbers represent people who were mothers, fathers, daughters, sons, husbands, wives, brothers, sisters, classmates, teammates, and best friends. The effects of these losses have cascaded through all aspects of our communities and across generations. To highlight the crisis and provide understanding and strategies to prevent the further loss of life, we have brought together a panel of experts with a wide range of knowledge and experience, from patient advocacy and prevention to front-line work to federal policy, from across the United States, to discuss the nationwide fentanyl crisis. |
Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2060: The SEARCH for Diabetes in Youth Study
Tönnies T , Brinks R , Isom S , Dabelea D , Divers J , Mayer-Davis EJ , Lawrence JM , Pihoker C , Dolan L , Liese AD , Saydah SH , D'Agostino RB , Hoyer A , Imperatore G . Diabetes Care 2022 46 (2) 313-320 OBJECTIVE: To project the prevalence and number of youths with diabetes and trends in racial and ethnic disparities in the U.S. through 2060. RESEARCH DESIGN AND METHODS: Based on a mathematical model and data from the SEARCH for Diabetes in Youth study for calendar years 2002-2017, we projected the future prevalence of type 1 and type 2 diabetes among youth aged <20 years while considering different scenarios of future trends in incidence. RESULTS: The number of youths with diabetes will increase from 213,000 (95% CI 209,000; 218,000) (type 1 diabetes 185,000, type 2 diabetes 28,000) in 2017 to 239,000 (95% CI 209,000; 282,000) (type 1 diabetes 191,000, type 2 diabetes 48,000) in 2060 if the incidence remains constant as observed in 2017. Corresponding relative increases were 3% (95% CI -9%; 21%) for type 1 diabetes and 69% (95% CI 43%; 109%) for type 2 diabetes. Assuming that increasing trends in incidence observed between 2002 and 2017 continue, the projected number of youths with diabetes will be 526,000 (95% CI 335,000; 893,000) (type 1 diabetes 306,000, type 2 diabetes 220,000). Corresponding relative increases would be 65% (95% CI 12%; 158%) for type 1 diabetes and 673% (95% CI 362%; 1,341%) for type 2 diabetes. In both scenarios, substantial widening of racial and ethnic disparities in type 2 diabetes prevalence are expected, with the highest prevalence among non-Hispanic Black youth. CONCLUSIONS: The number of youths with diabetes in the U.S. is likely to substantially increase in future decades, which emphasizes the need for prevention to attenuate this trend. |
Food insecurity, diet quality, and suboptimal diabetes management among US adults with diabetes
Casagrande SS , Bullard KM , Siegel KR , Lawrence JM . BMJ Open Diabetes Res Care 2022 10 (5) INTRODUCTION: A healthy diet is recommended to support diabetes management, including HbA1c, blood pressure, and cholesterol (ABC) control, but food insecurity is a barrier to consuming a healthy diet. We determined the prevalence of food insecurity and diet quality among US adults with diabetes and the associations with ABC management. RESEARCH DESIGN AND METHODS: Cross-sectional analyses were conducted among 2075 adults ≥20 years with diagnosed diabetes who participated in the 2013-2018 National Health and Nutrition Examination Surveys. Food insecurity was assessed using a standard questionnaire and diet quality was assessed using quartiles of the 2015 Healthy Eating Index. Adjusted ORs (aOR, 95% CI) were calculated from logistic regression models to determine the association between household food insecurity/diet quality and the ABCs while controlling for sociodemographic characteristics, healthcare utilization, smoking, medication for diabetes, blood pressure, or cholesterol, and body mass index. RESULTS: Overall, 17.6% of adults had food insecurity/low diet quality; 14.2% had food insecurity/high diet quality; 33.1% had food security/low diet quality; and 35.2% had food security/high diet quality. Compared with adults with food security/high diet quality, those with food insecurity/low diet quality were significantly more likely to have HbA1c ≥7.0% (aOR=1.85, 95% CI 1.23 to 2.80) and HbA1c ≥8.0% (aOR=1.79, 95% CI 1.04 to 3.08); food insecurity/high diet quality was significantly associated with elevated HbA1c; and food security/low diet quality with elevated A1c. CONCLUSIONS: Food insecurity, regardless of diet quality, was significantly associated with elevated A1c. For people with food insecurity, providing resources to reduce food insecurity could strengthen the overall approach to optimal diabetes management. |
Consensus on the key characteristics of immunotoxic agents as a basis for hazard identification
Germolec DR , Lebrec H , Anderson SE , Burleson GR , Cardenas A , Corsini E , Elmore SE , Kaplan BLF , Lawrence BP , Lehmann GM , Maier CC , McHale CM , Myers LP , Pallardy M , Rooney AA , Zeise L , Zhang L , Smith MT . Environ Health Perspect 2022 130 (10) 105001 BACKGROUND: Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents. OBJECTIVES: The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs. METHODS: A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity. DISCUSSION: KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800. |
A longitudinal assessment of diabetes autoantibodies in the SEARCH for diabetes in youth study
Merjaneh L , Dolan LM , Suerken CK , D'Agostino RJr , Imperatore G , Saydah S , Roberts A , Marcovina S , Mayer-Davis EJ , Dabelea D , Lawrence JM , Pihoker C . Pediatr Diabetes 2022 23 (7) 1027-1037 To assess changes in diabetes autoantibodies (DAs) over time in children and young adults with diabetes and determine whether observed changes were associated with demographic characteristics, clinical parameters and diabetes complications. Participants had DAs measured at baseline (10.3 ± 7.1 months after diabetes diagnosis) and at 12, 24 months and ≥5 years after the baseline measurement. At the ≥5-year follow-up, the presence of diabetes complications was assessed. We examined the associations between change in number of positive DAs and changes in individual DA status with the participants' characteristics and clinical parameters over time. Out of 4179 participants, 62% had longitudinal DA data and 51% had complications and longitudinal DA data. In participants with ≥1 baseline positive DA (n = 1699), 83.4% remained positive after 7.3 ± 2.3 years duration of diabetes. Decrease in number of positive DAs was associated with longer diabetes duration (p = 0.003 for 1 baseline positive DA; p < 0.001 for 2 baseline positive DAs) and younger age at diagnosis (p < 0.001 for 2 baseline positive DAs). No associations were found between change in number of positive DAs in participants with ≥1 baseline positive DA (n = 1391) and HbA1c, insulin dose, acute, or chronic complications after 7.7 ± 1.9 years duration of diabetes. DA status likely remains stable in the first 7 years after diabetes diagnosis. Younger age at diabetes diagnosis and longer duration were associated with less persistence of DAs. Measuring DAs after initial presentation may aid in diabetes classification but not likely in predicting the clinical course. |
'They can stigmatize you': a qualitative assessment of the influence of school factors on engagement in care and medication adherence among adolescents with HIV in Western Kenya
Wiggins L , O'Malley G , Wagner AD , Mutisya I , Wilson KS , Lawrence S , Moraa H , Kinuthia J , Itindi J , Muhenje O , Chen TH , Singa B , McGrath CJ , Ngugi E , Katana A , Ng Ang AL , John-Stewart G , Kholer P , Beima-Sofie K . Health Educ Res 2022 37 (5) 355-363 School-related factors may influence retention in care and adherence to antiretroviral therapy (ART) among adolescents with human immunodeficiency virus (HIV). We analyzed data from in-depth interviews with 40 adolescents with HIV (aged 14 -19 years), 40 caregivers of adolescents with HIV, and 4 focus group discussions with healthcare workers to evaluate contextual factors affecting adherence to ART and clinic attendance among adolescents, with a focus on the school environment. Informed by Anderson's Model of Health Services Utilization, transcripts were systematically coded and synthesized to identify school-related themes. All groups identified the school environment as a critical barrier to engagement in HIV care and medication adherence for adolescents with HIV. Adolescent participants reported inflexible school schedules and disclosure to school staff as the biggest challenges adhering to clinic appointments and ART. Adolescents described experiencing stigma and discrimination by peers and school staff and would adjust when, where and how often they took ART to avoid inadvertent disclosure. Boarding school students faced challenges because they had limited private space or time. Caregivers were often instrumental in navigating school permissions, including identifying a treatment supporter among school staff. Additional research engaging school staff may guide interventions for schools to reduce stigma and improve adherence and retention. |
Trends in glycemia between 2002 and 2016 among incident youth cohorts early in the course of type 1 diabetes: The SEARCH for Diabetes in Youth Study
Igudesman D , Reboussin BA , Souris KJ , Pihoker C , Dolan L , Lawrence JM , Saydah S , Dabelea D , Marcovina S , Clouet-Foraison N , Malik FS , Mayer-Davis EJ . J Diabetes Res 2022 2022 8554991 OBJECTIVE: Hyperglycemia early in the course of type 1 diabetes (T1D) may increase the risk of cardiometabolic complications later in life. We tested the hypothesis that there were temporal trends in population-level glycemia and insulin pump use near T1D diagnosis among incident youth cohorts diagnosed between 2002 and 2016. METHODS: Weighted and adjusted regression models were applied to data from the SEARCH for Diabetes in Youth study to analyze trends in hemoglobin A1c (HbA1c), suboptimal glycemia (HbA1c > 9% or not), and insulin pump use among youth with T1D within 30 months of diagnosis. We tested the interaction of year with race and ethnicity, sex, and insulin regimen to assess potential disparities. RESULTS: Among the 3,956 youth with T1D, there was a small, clinically insignificant reduction in HbA1c between 2002 (7.9% ± 1.5) and 2016 (7.8% ± 2.4) (fully adjusted change by year (-0.013% [95% CI -0.026, -0.0008], p = 0.04). The proportion of youth with suboptimal glycemia increased with each year, but the adjusted odds did not change. Insulin pump use increased more than fivefold. Although interaction effects of time with race and ethnicity, sex, and insulin regimen were not detected, in 2016, suboptimal glycemia was 4.3 and 1.8 times more prevalent among Black and Hispanic than among non-Hispanic White youth, respectively. CONCLUSIONS: There was not a clinically significant population-level improvement in glycemia across incident youth cohorts early in the course of T1D, despite severalfold increases in insulin pump use. Comprehensive clinical interventions to improve glycemia early in the T1D course and address disparities are urgently needed. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Litter Commensal Bacteria Can Limit the Horizontal Gene Transfer of Antimicrobial Resistance to Salmonella in Chickens.
Oladeinde A , Abdo Z , Zwirzitz B , Woyda R , Lakin SM , Press MO , Cox NA , Thomas JCth , Looft T , Rothrock MJJr , Zock G , Plumblee Lawrence J , Cudnik D , Ritz C , Aggrey SE , Liachko I , Grove JR , Wiersma C . Appl Environ Microbiol 2022 88 (9) e0251721 Fostering a "balanced" gut microbiome through the administration of beneficial microbes that can competitively exclude pathogens has gained a lot of attention and use in human and animal medicine. However, little is known about how microbes affect the horizontal gene transfer of antimicrobial resistance (AMR). To shed more light on this question, we challenged neonatal broiler chicks raised on reused broiler chicken litter-a complex environment made up of decomposing pine shavings, feces, uric acid, feathers, and feed-with Salmonella enterica serovar Heidelberg (S. Heidelberg), a model pathogen. Neonatal chicks challenged with S. Heidelberg and raised on reused litter were more resistant to S. Heidelberg cecal colonization than chicks grown on fresh litter. Furthermore, chicks grown on reused litter were at a lower risk of colonization with S. Heidelberg strains that encoded AMR on IncI1 plasmids. We used 16S rRNA gene sequencing and shotgun metagenomics to show that the major difference between chicks grown on fresh litter and those grown on reused litter was the microbiome harbored in the litter and ceca. The microbiome of reused litter samples was more uniform and enriched in functional pathways related to the biosynthesis of organic and antimicrobial molecules than that in fresh litter samples. We found that Escherichia coli was the main reservoir of plasmids encoding AMR and that the IncI1 plasmid was maintained at a significantly lower copy per cell in reused litter compared to fresh litter. These findings support the notion that commensal bacteria play an integral role in the horizontal transfer of plasmids encoding AMR to pathogens like Salmonella. IMPORTANCE Antimicrobial resistance spread is a worldwide health challenge, stemming in large part from the ability of microorganisms to share their genetic material through horizontal gene transfer. To address this issue, many countries and international organizations have adopted a One Health approach to curtail the proliferation of antimicrobial-resistant bacteria. This includes the removal and reduction of antibiotics used in food animal production and the development of alternatives to antibiotics. However, there is still a significant knowledge gap in our understanding of how resistance spreads in the absence of antibiotic selection and the role commensal bacteria play in reducing antibiotic resistance transfer. In this study, we show that commensal bacteria play a key role in reducing the horizontal gene transfer of antibiotic resistance to Salmonella, provide the identity of the bacterial species that potentially perform this function in broiler chickens, and also postulate the mechanism involved. |
Point prevalence of hip symptoms, radiographic, and symptomatic OA at five time points: The Johnston County Osteoarthritis Project, 1991-2018
Nelson AE , Hu D , Arbeeva L , Alvarez C , Cleveland RJ , Schwartz TA , Murphy LB , Helmick CG , Callahan LF , Renner JB , Jordan JM , Golightly YM . Osteoarthr Cartil Open 2022 4(2) (2) Objective: To describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). Design(s): Data were from 3068 JoCoOA participants who attended up to five study visits (1991-2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: "On most days, do you have pain, aching, or stiffness in your right/left hip?"; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2-4; 3) severe rHOA: KLG of 3-4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45-54, 55-64, 65-74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5-24.9; 25-29.9; 30+ kg/m2). Result(s): At the most recent follow-up (2017-2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. Conclusion(s): These updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort. Copyright © 2022 The Authors |
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