Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-10 (of 10 Records) |
Query Trace: Schmedes S [original query] |
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Concurrent outbreaks of hepatitis A, invasive meningococcal disease, and Mpox, Florida, USA, 2021-2022
Doyle TJ , Gumke M , Stanek D , Moore J , Buck B , Locksmith T , Tomson K , Schmedes S , Churchwell G , Hubsmith SJ , Krishnamoorthy B , Poschman K , Danforth B , Chacreton D . Emerg Infect Dis 2024 30 (4) 633-43 In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups. |
Containment of a Verona integron-encoded metallo-beta-lactamase-producing pseudomonas aeruginosa outbreak associated with an acute care hospital sink-Tennessee, 2018-2020
Chan A , Thure K , Tobey K , Shugart A , Schmedes S , Burks JAth , Hardin H , Moore C , Carpenter T , Brooks S , Gable P , Moulton Meissner H , McAllister G , Lawsin A , Laufer Halpin A , Spalding Walters M , Keaton A . Open Forum Infect Dis 2023 10 (5) ofad194 BACKGROUND: Contaminated healthcare facility wastewater plumbing is recognized as a source of carbapenemase-producing organism transmission. In August 2019, the Tennessee Department of Health (TDH) identified a patient colonized with Verona integron-encoded metallo-beta-lactamase-producing carbapenem-resistant Pseudomonas aeruginosa (VIM-CRPA). A record review revealed that 33% (4 of 12) of all reported patients in Tennessee with VIM had history of prior admission to acute care hospital (ACH) A intensive care unit (ICU) Room X, prompting further investigation. METHODS: A case was defined as polymerase chain reaction detection of bla(VIM) in a patient with prior admission to ACH A from November 2017 to November 2020. The TDH performed point prevalence surveys, discharge screening, onsite observations, and environmental testing at ACH A. The VIM-CRPA isolates underwent whole-genome sequencing (WGS). RESULTS: In a screening of 44% (n = 11) of 25 patients admitted to Room X between January and June 2020, we identified 36% (n = 4) colonized with VIM-CRPA, resulting in 8 cases associated with Room X from March 2018 to June 2020. No additional cases were identified in 2 point-prevalence surveys of the ACH A ICU. Samples from the bathroom and handwashing sink drains in Room X grew VIM-CRPA; all available case and environmental isolates were found to be ST253 harboring bla(VIM-1) and to be closely related by WGS. Transmission ended after implementation of intensive water management and infection control interventions. CONCLUSIONS: A single ICU room's contaminated drains were associated with 8 VIM-CRPA cases over a 2-year period. This outbreak highlights the need to include wastewater plumbing in hospital water management plans to mitigate the risk of transmission of antibiotic-resistant organisms to patients. |
Predicting Plasmodium falciparum infection status in blood using a multiplexed bead-based antigen detection assay and machine learning approaches.
Schmedes SE , Dimbu RP , Steinhardt L , Lemoine JF , Chang MA , Plucinski M , Rogier E . PLoS One 2022 17 (9) e0275096 BACKGROUND: Plasmodium blood-stage infections can be identified by assaying for protein products expressed by the parasites. While the binary result of an antigen test is sufficient for a clinical result, greater nuance can be gathered for malaria infection status based on quantitative and sensitive detection of Plasmodium antigens and machine learning analytical approaches. METHODS: Three independent malaria studies performed in Angola and Haiti enrolled persons at health facilities and collected a blood sample. Presence and parasite density of P. falciparum infection was determined by microscopy for a study in Angola in 2015 (n = 193), by qRT-PCR for a 2016 study in Angola (n = 208), and by qPCR for a 2012-2013 Haiti study (n = 425). All samples also had bead-based detection and quantification of three Plasmodium antigens: pAldolase, pLDH, and HRP2. Decision trees and principal component analysis (PCA) were conducted in attempt to categorize P. falciparum parasitemia density status based on continuous antigen concentrations. RESULTS: Conditional inference trees were trained using the known P. falciparum infection status and corresponding antigen concentrations, and PCR infection status was predicted with accuracies ranging from 73-96%, while level of parasite density was predicted with accuracies ranging from 59-72%. Multiple decision nodes were created for both pAldolase and HRP2 antigens. For all datasets, dichotomous infectious status was more accurately predicted when compared to categorization of different levels of parasite densities. PCA was able to account for a high level of variance (>80%), and distinct clustering was found in both dichotomous and categorical infection status. CONCLUSIONS: This pilot study offers a proof-of-principle of the utility of machine learning approaches to assess P. falciparum infection status based on continuous concentrations of multiple Plasmodium antigens. |
Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance.
Moriarty LF , Nkoli PM , Likwela JL , Mulopo PM , Sompwe EM , Rika JM , Mavoko HM , Svigel SS , Jones S , Ntamabyaliro NY , Kaputu AK , Lucchi N , Subramaniam G , Niang M , Sadou A , Ngoyi DM , Muyembe Tamfum JJ , Schmedes SE , Plucinski MM , Chowell-Puente G , Halsey ES , Kahunu GM . Am J Trop Med Hyg 2021 105 (4) 1067-1075 Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted. |
Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014-2018.
Schmedes SE , Patel D , Dhal S , Kelley J , Svigel SS , Dimbu PR , Adeothy AL , Kahunu GM , Nkoli PM , Beavogui AH , Kariuki S , Mathanga DP , Koita O , Ishengoma D , Mohamad A , Hawela M , Moriarty LF , Samuels AM , Gutman J , Plucinski MM , Udhayakumar V , Zhou Z , Lucchi NW , Venkatesan M , Halsey ES , Talundzic E . Emerg Infect Dis 2021 27 (7) 1902-1908 The spread of drug resistance to antimalarial treatments poses a serious public health risk globally. To combat this risk, molecular surveillance of drug resistance is imperative. We report the prevalence of mutations in the Plasmodium falciparum kelch 13 propeller domain associated with partial artemisinin resistance, which we determined by using Sanger sequencing samples from patients enrolled in therapeutic efficacy studies from 9 sub-Saharan countries during 2014-2018. Of the 2,865 samples successfully sequenced before treatment (day of enrollment) and on the day of treatment failure, 29 (1.0%) samples contained 11 unique nonsynonymous mutations and 83 (2.9%) samples contained 27 unique synonymous mutations. Two samples from Kenya contained the S522C mutation, which has been associated with delayed parasite clearance; however, no samples contained validated or candidate artemisinin-resistance mutations. |
Targeted deep amplicon sequencing of antimalarial resistance markers in Plasmodium falciparum isolates from Cameroon.
L'Episcopia M , Kelley J , Dongho BGD , Patel D , Schmedes S , Ravishankar S , Perrotti E , Modiano D , Lucchi NW , Russo G , Talundzic E , Severini C . Int J Infect Dis 2021 107 234-241 BACKGROUND: Recent studies show the first emergence of the R561H artemisinin-associated resistance marker in Africa, which highlights the importance of continued molecular surveillance to assess the selection and spread of this and other drug resistance markers in the region. METHOD: In this study, we used targeted deep amplicon sequencing (TADS) of 116 isolates collected in two areas of Cameroon to genotype the major drug resistance genes k13, crt, mdr1, dhfr, dhps, and the cytochrome b (cytb) in P. falciparum. RESULTS: No confirmed or associated artemisinin resistance markers were observed in Pfk13. In comparison, both major and minor alleles associated with drug resistance were found in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. Notably, a high frequency of other non-synonymous mutations was observed across all the genes, except Pfcytb, suggesting continued selection pressure. CONCLUSIONS: The results from this study support the continued use of artemisinin combination therapy (ACT) for treatment and administration of sulphadoxine-pyrimethamine for intermittent preventive therapy in pregnant women and for seasonal chemoprevention in these study sites in Cameroon. |
Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol.
L'Episcopia M , Kelley J , Patel D , Schmedes S , Ravishankar S , Menegon M , Perrotti E , Nurahmed AM , Talha AA , Nour BY , Lucchi N , Severini C , Talundzic E . Parasit Vectors 2020 13 (1) 137 BACKGROUND: Routine molecular surveillance for imported drug-resistant malaria parasites to the USA and European Union is an important public health activity. The obtained molecular data are used to help keep chemoprophylaxis and treatment guidelines up to date for persons traveling to malaria endemic countries. Recent advances in next-generation sequencing (NGS) technologies provide a new and effective way of tracking malaria drug-resistant parasites. METHODS: As part of a technology transfer arrangement between the CDC Malaria Branch and the Istituto Superiore di Sanita (ISS), Rome, Italy, the recently described Malaria Resistance Surveillance (MaRS) protocol was used to genotype 148 Plasmodium falciparum isolates from Eritrea for kelch 13 (k13) and cytochrome b (cytb) genes, molecular markers associated with resistance to artemisinin (ART) and atovaquone/proguanil (AP), respectively. RESULTS: Spanning the full-length k13 gene, seven non-synonymous single nucleotide polymorphisms (SNPs) were found (K189N, K189T, E208K, D281V, E401Q, R622I and T535M), of which none have been associated with artemisinin resistance. No mutations were found in cytochrome b. CONCLUSION: All patients successfully genotyped carried parasites susceptible to ART and AP treatment. Future studies between CDC Malaria Branch and ISS are planned to expand the MaRS system, including data sharing, in an effort to maintain up to date treatment guidelines for travelers to malaria endemic countries. |
Using the Plasmodium mitochondrial genome for classifying mixed-species infections and inferring the geographical origin of P. falciparum parasites imported to the U.S.
Schmedes SE , Patel D , Kelley J , Udhayakumar V , Talundzic E . PLoS One 2019 14 (4) e0215754 The ability to identify mixed-species infections and track the origin of Plasmodium parasites can further enhance the development of treatment and prevention recommendations as well as outbreak investigations. Here, we explore the utility of using the full Plasmodium mitochondrial genome to classify Plasmodium species, detect mixed infections, and infer the geographical origin of imported P. falciparum parasites to the United States (U.S.). Using the recently developed standardized, high-throughput Malaria Resistance Surveillance (MaRS) protocol, the full Plasmodium mitochondrial genomes of 265 malaria cases imported to the U.S. from 2014-2017 were sequenced and analyzed. P. falciparum infections were found in 94.7% (251/265) of samples. Five percent (14/265) of samples were identified as mixed- Plasmodium species or non-P. falciparum, including P. vivax, P. malariae, P. ovale curtisi, and P. ovale wallikeri. P. falciparum mitochondrial haplotypes analysis revealed greater than eighteen percent of samples to have at least two P. falciparum mitochondrial genome haplotypes, indicating either heteroplasmy or multi-clonal infections. Maximum-likelihood phylogenies of 912 P. falciparum mitochondrial genomes with known country origin were used to infer the geographical origin of thirteen samples from persons with unknown travel histories as: Africa (country unspecified) (n = 10), Ghana (n = 1), Southeast Asia (n = 1), and the Philippines (n = 1). We demonstrate the utility and current limitations of using the Plasmodium mitochondrial genome to classify samples with mixed-infections and infer the geographical origin of imported P. falciparum malaria cases to the U.S. with unknown travel history. |
A next-generation sequencing and bioinformatics protocol for Malaria drug Resistance marker Surveillance (MaRS).
Talundzic E , Ravishankar S , Kelly J , Patel D , Plucinski M , Schmedes S , Ljolje D , Clemons B , Madison-Antenucci S , Arguin PM , Lucchi N , Vannberg F , Udhayakumar V . Antimicrob Agents Chemother 2018 62 (4) The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug resistant parasites. To take advantage of this technology an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance in P. falciparum, called Malaria Resistance Surveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing. MaRS enables researchers to simultaneously collect data on allele frequencies of multiple full-length P. falciparum drug resistance genes (crt, mdr1, k13, dhfr, dhps, and cytochrome b) as well as the mitochondrial genome. Information is captured at the individual patient level for both known and potential new single nucleotide polymorphisms associated with drug resistance. MaRS pipeline was validated using 245 imported malaria cases that were reported to the Centers for Disease Control and Prevention (CDC). The chloroquine resistant crt CV IET genotype was observed in 42% of samples, the highly pyrimethamine resistant triple mutant dhpsIRN in 92% of samples, and the sulfadoxine resistant dhps S GE AA in 26% of samples. The mdr1 N F SND genotype was found in 40% of samples. With the exception of two cases imported from Cambodia, no artemisinin resistant K13 alleles were identified and 99% of patients carried parasites susceptible to atovaquone-proguanil. Our goal is to implement MaRS at the CDC for routine surveillance of imported malaria cases in the U.S. and aid in the adoption of this system in participating state public health laboratories as well as global partners. |
Validation of high throughput sequencing and microbial forensics applications.
Budowle B , Connell ND , Bielecka-Oder A , Colwell RR , Corbett CR , Fletcher J , Forsman M , Kadavy DR , Markotic A , Morse SA , Murch RS , Sajantila A , Schmedes SE , Ternus KL , Turner SD , Minot S . Investig Genet 2014 5 9 High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security. |
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