Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-30 (of 30 Records) |
Query Trace: Laurent C [original query] |
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Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons
Owuor DC , de Laurent ZR , Nyawanda BO , Emukule GO , Kondor R , Barnes JR , Nokes DJ , Agoti CN , Chaves SS . Sci Rep 2023 13 (1) 22342 Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines. |
Lessons learned from applying a monitoring and evaluation framework to economic, social, and other health impacts of the COVID-19 pandemic
Laurent AA , Vo L , Wong EY . Public Health Rep 2023 139 (1) 333549231208489 Individual and community-level COVID-19 mitigation policies can have effects beyond direct COVID-19 health outcomes, including social, behavioral, and economic outcomes. These social, behavioral, and economic outcomes can extend beyond the pandemic period and have disparate effects on populations. Public Health-Seattle & King County (PHSKC) built on the Centers for Disease Control and Prevention's community mitigation strategy framework to create a local project tracking near-real-time data to understand factors affected by mitigation approaches, inform decision-making, and monitor and evaluate community-level disparities during the pandemic. This case study describes the framework and lessons learned from PHSKC's collation, use, and dissemination of local data from 20 data sources to guide community and public health decision-making. Social, behavioral, economic, and health indicators were regularly updated and disseminated through interactive dashboards and products that examined data in the context of applicable policies. Data disaggregated by demographic characteristics and geography highlighted inequities, but not all datasets contained the same details; local surveys or qualitative data were used to fill gaps. Project outcomes included informing city and county emergency response planning related to implementation of financial and food assistance programs. Key lessons learned included the need to (1) build on existing processes and use automated processes and (2) partner with other sectors to use nontraditional public health data for active dissemination and data disaggregation and for real-time data contextualized by policy changes. This project provided programs and communities with timely, reliable data to understand where to invest recovery funding. A similar framework could position other health departments to examine social and economic effects during future public health emergencies. |
Characterizing the countrywide epidemic spread of influenza A(H1N1)pdm09 virus in Kenya between 2009 and 2018 (preprint)
Owuor DC , de Laurent ZR , Kikwai GK , Mayieka LM , Ochieng M , Müller NF , Otieno NA , Emukule GO , Hunsperger EA , Garten R , Barnes JR , Chaves SS , Nokes DJ , Agoti CN . medRxiv 2021 2021.03.30.21254587 Background The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data is lacking.Methods We isolated, sequenced, and analyzed 383 influenza A(H1N1)pdm09 viral genomes isolated from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods.Results The transmission dynamics of influenza A(H1N1)pdm09 virus in Kenya was characterized by: (i) multiple virus introductions into Kenya over the study period, although these were remarkably few, with only a few of those introductions instigating seasonal epidemics that then established local transmission clusters; (ii) persistence of transmission clusters over several epidemic seasons across the country; (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres; (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-11 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-17; and (v) virus migration from multiple geographical regions to multiple geographical destinations in Kenya.Conclusion Considerable influenza virus diversity circulates within Africa, as demonstrated in this report, including virus lineages that are unique to the region, which may be capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.Competing Interest StatementThe authors have declared no competing interest.Funding StatementFunding: The authors D.C.O. and C.N.A. were supported by the Initiative to Develop African Research Leaders (IDeAL) through the DELTAS Africa Initiative [DEL-15-003]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The study was also part funded by a Wellcome Trust grant [1029745] and the USA CDC grant [GH002133]. N.F.M. is supported by the Swiss National Science Foundation (PZEZP3_191891). This paper is published with the permission of the Director of KEMRI.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Kenya Medical Research Institute (KEMRI) and KEMRI-Wellcome Trust Research Programme Scientific and Ethics Review Unit (SERU), which is mandated to provide ethical approval for research work conducted in Kenya, provided ethical approval for the studies which collected and archived the samples used in these studies. These were approved under the following Scientific Steering Committee (SSC) approvals: 1. SSC No. 1899, SSC No. 2558 and SSC No. 2692; 2. KEMRI-Wellcome Trust Research Programme SSC No. 1055 and SSC No. 1433.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as Clini alTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll generated sequence data were deposited in the Global Initiative on Sharing All Influenza Data (GISAID). https://github.com/DCollinsOwuor/H1N1pdm09_Kenya_Phylodynamics/tree/main/Data/. |
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. |
Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons (preprint)
Owuor DC , de Laurent ZR , Nyawanda BO , Emukule GO , Kondor R , Barnes JR , Nokes DJ , Agoti CN , Chaves SS . medRxiv 2022 13 Background. Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. Methods. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and determinants of clinical outcome. Results. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity reduced with increase in age among children aged <5 years. Conclusion. Our study highlights the utility of genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on the severity of circulating strains could improve selection of influenza strains for inclusion in vaccines. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
The genomic epidemiology of SARS-CoV-2 variants of concern in Kenya (preprint)
Githinji G , Lambisia AW , Omah I , O'Toole A , Mohamed KS , de Laurent ZR , Makori TO , Mwanga M , Mburu MW , Morobe JM , Ong'era EM , Ndwiga L , Gathii K , Thiongo K , Omuoyo DWO , Chepkorir E , Musyoki J , Kingwara L , Matoke D , Oyola SO , Onyango C , Waitumbi J , Bulimo W , Khamadi S , Kiiru JNO , Kinyanjui S , Cotten M , Tsofa B , Ochola-Oyier I , Rambaut A , Nokes DJ , Bejon P , Agoti C . medRxiv 2022 27 The emergence and establishment of SARS-CoV-2 variants of concern presented a major global public health crisis across the world. There were six waves of SARSCoV-2 cases in Kenya that corresponded with the introduction and eventual dominance of the major SARS-COV-2 variants of concern, excepting the first 2 waves that were both wild-type virus. We estimate that more than 1000 SARS-CoV-2 introductions occurred in the two-year epidemic period (March 2020 - September 2022) and a total of 930 introductions were associated with variants of concern namely Beta (n=78), Alpha(n=108), Delta(n=239) and Omicron (n=505). A total of 29 introductions were associated with A.23.1 variant that circulated in high frequencies in Uganda and Rwanda. The actual number of introductions is likely to be higher than these conservative estimates due to limited genomic sequencing. Our data suggested that cryptic transmission was usually underway prior to the first real-time identification of a new variant, and that multiple introductions were responsible. Following emergence of each VOC and subsequent introduction, transmission patterns were associated with hotspots of transmission in Coast, Nairobi and Western Kenya and follows established land and air transport corridors. Understanding the introduction and dispersal of major circulating variants and identifying the sources of new introductions is important to inform public health control strategies within Kenya and the larger East-African region. Border control and case finding reactive to new variants is unlikely to be a successful control strategy. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Phylogenomic analysis uncovers a 9-year variation of Uganda influenza type-A strains from the WHO-recommended vaccines and other Africa strains.
Nabakooza G , Owuor DC , de Laurent ZR , Galiwango R , Owor N , Kayiwa JT , Jjingo D , Agoti CN , Nokes DJ , Kateete DP , Kitayimbwa JM , Frost SDW , Lutwama JJ . Sci Rep 2023 13 (1) 5516 Genetic characterisation of circulating influenza viruses directs annual vaccine strain selection and mitigation of infection spread. We used next-generation sequencing to locally generate whole genomes from 116 A(H1N1)pdm09 and 118 A(H3N2) positive patient swabs collected across Uganda between 2010 and 2018. We recovered sequences from 92% (215/234) of the swabs, 90% (193/215) of which were whole genomes. The newly-generated sequences were genetically and phylogenetically compared to the WHO-recommended vaccines and other Africa strains sampled since 1994. Uganda strain hemagglutinin (n = 206), neuraminidase (n = 207), and matrix protein (MP, n = 213) sequences had 95.23-99.65%, 95.31-99.79%, and 95.46-100% amino acid similarity to the 2010-2020 season vaccines, respectively, with several mutated hemagglutinin antigenic, receptor binding, and N-linked glycosylation sites. Uganda influenza type-A virus strains sequenced before 2016 clustered uniquely while later strains mixed with other Africa and global strains. We are the first to report novel A(H1N1)pdm09 subclades 6B.1A.3, 6B.1A.5(a,b), and 6B.1A.6 (± T120A) that circulated in Eastern, Western, and Southern Africa in 2017-2019. Africa forms part of the global influenza ecology with high viral genetic diversity, progressive antigenic drift, and local transmissions. For a continent with inadequate health resources and where social distancing is unsustainable, vaccination is the best option. Hence, African stakeholders should prioritise routine genome sequencing and analysis to direct vaccine selection and virus control. |
Using population mobility patterns to adapt COVID-19 response strategies in 3 East Africa countries
Merrill RD , Kilamile F , White M , Eurien D , Mehta K , Ojwang J , Laurent-Comlan M , Babigumira PA , Nakiire L , Boos A , Gatei W , Harris JR , Magazani A , Ocom F , Ssekubugu R , Kigozi G , Senyana F , Iyese FB , Elyanu PJ , Ward S , Makumbi I , Muruta A , McIntyre E , Massa K , Ario AR , Mayinja H , Remidius K , Ndungi DN . Emerg Infect Dis 2022 28 (13) S105-s113 The COVID-19 pandemic spread between neighboring countries through land, water, and air travel. Since May 2020, ministries of health for the Democratic Republic of the Congo, Tanzania, and Uganda have sought to clarify population movement patterns to improve their disease surveillance and pandemic response efforts. Ministry of Health-led teams completed focus group discussions with participatory mapping using country-adapted Population Connectivity Across Borders toolkits. They analyzed the qualitative and spatial data to prioritize locations for enhanced COVID-19 surveillance, community outreach, and cross-border collaboration. Each country employed varying toolkit strategies, but all countries applied the results to adapt their national and binational communicable disease response strategies during the pandemic, although the Democratic Republic of the Congo used only the raw data rather than generating datasets and digitized products. This 3-country comparison highlights how governments create preparedness and response strategies adapted to their unique sociocultural and cross-border dynamics to strengthen global health security. |
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. |
The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis
Walker TM , Fowler PW , Knaggs J , Hunt M , Peto TE , Walker AS , Crook DW , Walker TM , Miotto P , Cirillo DM , Kser CU , Knaggs J , Iqbal Z , Hunt M , Chindelevitch L , Farhat MR , Comas I , Comas I , Posey J , Omar SV , Peto TE , Walker AS , Crook DW , Suresh A , Uplekar S , Laurent S , Colman RE , Rodwell TC , Nathanson CM , Zignol M , Ismail N , Rodwell TC , Walker AS , Steyn AJC , Lalvani A , Baulard A , Christoffels A , Mendoza-Ticona A , Trovato A , Skrahina A , Lachapelle AS , Brankin A , Piatek A , GibertoniCruz A , Koch A , Cabibbe AM , Spitaleri A , Brandao AP , Chaiprasert A , Suresh A , Barbova A , VanRie A , Ghodousi A , Bainomugisa A , Mandal A , Roohi A , Javid B , Zhu B , Letcher B , Rodrigues C , Nimmo C , Nathanson CM , Duncan C , Coulter C , Utpatel C , Liu C , Grazian C , Kong C , Kser CU , Wilson DJ , Cirillo DM , Matias D , Jorgensen D , Zimenkov D , Chetty D , Moore DA , Clifton DA , Crook DW , vanSoolingen D , Liu D , Kohlerschmidt D , Barreira D , Ngcamu D , SantosLazaro ED , Kelly E , Borroni E , Roycroft E , Andre E , Bttger EC , Robinson E , Menardo F , Mendes FF , Jamieson FB , Coll F , Gao GF , Kasule GW , Rossolini GM , Rodger G , Smith EG , Meintjes G , Thwaites G , Hoffmann H , Albert H , Cox H , Laurenson IF , Comas I , Arandjelovic I , Barilar I , Robledo J , Millard J , Johnston J , Posey J , Andrews JR , Knaggs J , Gardy J , Guthrie J , Taylor J , Werngren J , Metcalfe J , Coronel J , Shea J , Carter J , Pinhata JM , Kus JV , Todt K , Holt K , Nilgiriwala KS , Ghisi KT , Malone KM , Faksri K , Musser KA , Joseph L , Rigouts L , Chindelevitch L , Jarrett L , Grandjean L , Ferrazoli L , Rodrigues M , Farhat M , Schito M , Fitzgibbon MM , Loemb MM , Wijkander M , Ballif M , Rabodoarivelo MS , Mihalic M , Wilcox M , Hunt M , Zignol M , Merker M , Egger M , O'Donnell M , Caws M , Wu MH , Whitfield MG , Inouye M , Mansj M , DangThi MH , Joloba M , Kamal SM , Okozi N , Ismail N , Mistry N , Hoang NN , Rakotosamimanana N , Paton NI , Rancoita PMV , Miotto P , Lapierre P , Hall PJ , Tang P , Claxton P , Wintringer P , Keller PM , Thai PVK , Fowler PW , Supply P , Srilohasin P , Suriyaphol P , Rathod P , Kambli P , Groenheit R , Colman RE , Ong RTH , Warren RM , Wilkinson RJ , Diel R , Oliveira RS , Khot R , Jou R , Tahseen S , Laurent S , Gharbia S , Kouchaki S , Shah S , Plesnik S , Earle SG , Dunstan S , Hoosdally SJ , Mitarai S , Gagneux S , Omar SV , Yao SY , GrandjeanLapierre S , Battaglia S , Niemann S , Pandey S , Uplekar S , Halse TA , Cohen T , Cortes T , Prammananan T , Kohl TA , Thuong NTT , Teo TY , Peto TEA , Rodwell TC , William T , Walker TM , Rogers TR , Surve U , Mathys V , Furi V , Cook V , Vijay S , Escuyer V , Dreyer V , Sintchenko V , Saphonn V , Solano W , Lin WH , vanGemert W , He W , Yang Y , Zhao Y , Qin Y , Xiao YX , Hasan Z , Iqbal Z , Puyen ZM , CryPticConsortium theSeq , Treat Consortium . Lancet Microbe 2022 3 (4) e265-e273 Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018.
Owuor DC , de Laurent ZR , Kikwai GK , Mayieka LM , Ochieng M , Müller NF , Otieno NA , Emukule GO , Hunsperger EA , Garten R , Barnes JR , Chaves SS , Nokes DJ , Agoti CN . Viruses 2021 13 (10) The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (R(e)) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009-2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012-2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions. |
The performance of immunoassays to measure antibodies to the Chlamydia trachomatis antigen Pgp3 in different epidemiological settings for trachoma
Gwyn S , Bethea D , Laurent C , Martin D . Am J Trop Med Hyg 2021 105 (5) 1362-1367 Programs to eliminate trachoma as a public health problem use prevalence of the clinical sign trachomatous inflammation-follicular (TF) in 1- to 9-year-olds in endemic districts to make decisions to begin or end mass drug administration with azithromycin. Trachomatous inflammation-follicular is used as a proxy for transmission of ocular Chlamydia trachomatis infection. Long-term monitoring of previously endemic districts for recrudescence of ocular C. trachomatis infection would benefit from a simple blood test that could be integrated with other public health programs. In this study, we evaluated multiple tests to measure antibodies against the C. trachomatis antigen Pgp3-a multiplex bead assay (MBA), an ELISA, and two versions of a lateral flow assay (LFA)-in four districts of the Amhara region of Ethiopia with varying levels of TF. Seroprevalence and seroconversion rate (SCR) results were proportional to TF prevalence by district for most tests, with the notable exception of the LFA using colloidal gold as the developing reagent. Changing the test developing reagent to black latex improved agreement between serological measures and TF prevalence and in inter-rater agreement. Seroconversion rate estimates using data derived from the LFA-gold assay were inconsistent with the shape of the age-seroprevalence curve, which did not increase in older ages. These data revealed potential complications with using SCR that will need further evaluation. Data from MBA, ELISA, and LFA with the black test line showed good agreement with each other and proportionality to TF estimates, providing further data that serology has potential utility for trachoma surveillance. |
High-throughput detection of eukaryotic parasites and arboviruses in mosquitoes.
Cannon Matthew V, Bogale Haikel N, Bhalerao Devika, Keita Kalil, Camara Denka, Barry Yaya, Keita Moussa, Coulibaly Drissa, Kone Abdoulaye K, Doumbo Ogobara K, Thera Mahamadou A, Plowe Christopher V, Travassos Mark A, Irish Seth R, Yeroshefsky Joshua, Dorothy Jeannine, Prendergast Brian, St Laurent Brandyce, Fritz Megan L, Serre David. Biology open 2021 10(7) . Biology open 2021 10(7) Cannon Matthew V, Bogale Haikel N, Bhalerao Devika, Keita Kalil, Camara Denka, Barry Yaya, Keita Moussa, Coulibaly Drissa, Kone Abdoulaye K, Doumbo Ogobara K, Thera Mahamadou A, Plowe Christopher V, Travassos Mark A, Irish Seth R, Yeroshefsky Joshua, Dorothy Jeannine, Prendergast Brian, St Laurent Brandyce, Fritz Megan L, Serre David. Biology open 2021 10(7) |
High-throughput Detection of Eukaryotic Parasites and Arboviruses in Mosquitoes
Cannon MV , Bogale HN , Bhalerao D , Keita K , Camara D , Barry Y , Keita M , Coulibaly D , Kone AK , Doumbo OK , Thera MA , Plowe CV , Travassos MA , Irish SR , Yeroshefsky J , Dorothy J , Prendergast B , Laurent BS , Fritz ML , Serre D . Biol Open 2021 10 (7) Vector-borne pathogens cause many human infectious diseases and are responsible for high mortality and morbidity throughout the world. They can also cause livestock epidemics with dramatic social and economic consequences. Due to its high costs, vector-borne disease surveillance is often limited to current threats, and the investigation of emerging pathogens typically occurs after the reports of clinical cases. Here, we use high-throughput sequencing to detect and identify a wide range of parasites and viruses carried by mosquitoes from Cambodia, Guinea, Mali and Maryland. We apply this approach to individual Anopheles mosquitoes as well as pools of mosquitoes captured in traps; and compare the outcomes of this assay when applied to DNA or RNA. We identified known human and animal pathogens and mosquito parasites belonging to a wide range of taxa, as well as novel DNA sequences from previously uncharacterized organisms. Our results also revealed that analysis of the content of an entire trap could be an efficient approach to monitor and identify rare vector-borne pathogens in large surveillance studies. Overall, we describe a high-throughput and easy-to-customize assay to screen for a wide-range of pathogens and efficiently complement current vector-borne disease surveillance approaches. |
Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.
Washington NL , Gangavarapu K , Zeller M , Bolze A , Cirulli ET , Schiabor Barrett KM , Larsen BB , Anderson C , White S , Cassens T , Jacobs S , Levan G , Nguyen J , Ramirez JM3rd , Rivera-Garcia C , Sandoval E , Wang X , Wong D , Spencer E , Robles-Sikisaka R , Kurzban E , Hughes LD , Deng X , Wang C , Servellita V , Valentine H , De Hoff P , Seaver P , Sathe S , Gietzen K , Sickler B , Antico J , Hoon K , Liu J , Harding A , Bakhtar O , Basler T , Austin B , MacCannell D , Isaksson M , Febbo PG , Becker D , Laurent M , McDonald E , Yeo GW , Knight R , Laurent LC , de Feo E , Worobey M , Chiu CY , Suchard MA , Lu JT , Lee W , Andersen KG . Cell 2021 184 (10) 2587-2594 e7 The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality. |
Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.
Bastard P , Michailidis E , Hoffmann HH , Chbihi M , Le Voyer T , Rosain J , Philippot Q , Seeleuthner Y , Gervais A , Materna M , de Oliveira PMN , Maia MLS , Dinis Ano Bom AP , Azamor T , Araújo da Conceição D , Goudouris E , Homma A , Slesak G , Schäfer J , Pulendran B , Miller JD , Huits R , Yang R , Rosen LB , Bizien L , Lorenzo L , Chrabieh M , Erazo LV , Rozenberg F , Jeljeli MM , Béziat V , Holland SM , Cobat A , Notarangelo LD , Su HC , Ahmed R , Puel A , Zhang SY , Abel L , Seligman SJ , Zhang Q , MacDonald MR , Jouanguy E , Rice CM , Casanova JL . J Exp Med 2021 218 (4) Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. One 13-yr-old patient had AR complete IFNAR2 deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 yr had high titers of circulating auto-Abs against at least 14 of the 17 individual type I IFNs. These antibodies were recently shown to underlie at least 10% of cases of life-threatening COVID-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-α2 against YFV vaccine strains. AR IFNAR1 or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV vaccination. |
Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection.
Vergara C , Duggal P , Thio CL , Valencia A , Brien TRO , Latanich R , Timp W , Johnson EO , Kral AH , Mangia A , Goedert JJ , Piazzola V , Mehta SH , Kirk GD , Peters MG , Donfield SM , Edlin BR , Busch MP , Alexander G , Murphy EL , Kim AY , Lauer GM , Chung RT , Cramp ME , Cox AL , Khakoo SI , Rosen HR , Alric L , Wheelan SJ , Wojcik GL , Thomas DL , Taub MA . Genes Immun 2020 21 (5) 348-359 Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10(-04)) and rs8099917 (P value = 5.5 × 10(-04)). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10(-05)). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10(-04)). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917. |
Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls
Dobraca D , Laurent CA , Greenspan LC , Hiatt RA , Sjodin A , Kushi LH , Windham GC . Environ Epidemiol 2020 4 (4) e0102 BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, environmental chemicals that may have endocrine disrupting capabilities. We investigated whether childhood exposure to PAHs was associated with adiposity and pubertal timing in a longitudinal study of 404 girls enrolled in the Northern California site of the Breast Cancer and the Environment Research Program cohort. METHODS: Baseline urinary samples from girls aged 6-8-years-old were assayed for 2-naphthol, fluorene metabolites, phenanthrene metabolites, 1-hydroxypyrene, and sum of PAH metabolites. Mixed-effects linear models were used to estimate how concentrations of PAH metabolites were related to changes in girl's body mass index (BMI) and waist-to-height ratio from age 7 through 16 years old. Accelerated failure time models were used to estimate age of pubertal onset (Tanner stages 2 or higher for breast and pubic hair development). RESULTS: Higher adiposity measurements among high tertiles of baseline PAH metabolites were evident at age 7 years old and increased thereafter (i.e., BMI for all PAH metabolites, waist-to-height ratio for fluorene and phenanthrene metabolites) or leveled off (i.e., waist-to-height ratio for 2-naphthol, 1-hydroxypyrene, sum of PAHs). Among girls overweight/obese at baseline, median age of breast development onset for high tertiles was 9.1-9.4 years old compared with 10-10.2 years old for low tertiles for all PAH metabolites; in contrast, found no association or slightly later onset of breast development for girls with normal weight at baseline. DISCUSSION: These results suggest that exposure to specific PAHs during childhood may influence adiposity throughout adolescence and effect pubertal timing. |
Multistate outbreak of Salmonella infections linked to raw turkey products - United States, 2017-2019
Hassan R , Buuck S , Noveroske D , Medus C , Sorenson A , Laurent J , Rotstein D , Schlater L , Freiman J , Douris A , Simmons M , Donovan D , Henderson J , Tewell M , Snyder K , Oni O , Von Stein D , Dassie K , Leeper M , Adediran A , Dowell N , Gieraltowski L , Basler C . MMWR Morb Mortal Wkly Rep 2019 68 (46) 1045-1049 During 2018–2019, CDC, local and state public health partners, the U.S. Department of Agriculture (USDA), and the Food and Drug Administration (FDA) investigated a multistate outbreak of 356 Salmonella Reading infections from 42 states and the District of Columbia (DC) linked to turkey. The outbreak strain was isolated from raw turkey products, raw turkey pet food, and live turkeys. In July 2018, CDC and USDA’s Food Safety and Inspection Service (FSIS) shared outbreak investigation results with representatives from the U.S. turkey industry, engaging with an industry group rather than a specific company for the first time during an outbreak, and CDC issued a public investigation notice. During the investigation, four recalls of turkey products were issued. Evidence suggested that the outbreak strain of Salmonella was widespread in the turkey industry, and therefore, interventions should target all parts of the supply chain, including slaughter and processing facilities and upstream farm sources. |
New filovirus disease classification and nomenclature.
Kuhn JH , Adachi T , Adhikari NKJ , Arribas JR , Bah IE , Bausch DG , Bhadelia N , Borchert M , Brantsaeter AB , Brett-Major DM , Burgess TH , Chertow DS , Chute CG , Cieslak TJ , Colebunders R , Crozier I , Davey RT , de Clerck H , Delgado R , Evans L , Fallah M , Fischer WA 2nd , Fletcher TE , Fowler RA , Grunewald T , Hall A , Hewlett A , Hoepelman AIM , Houlihan CF , Ippolito G , Jacob ST , Jacobs M , Jakob R , Jacquerioz FA , Kaiser L , Kalil AC , Kamara RF , Kapetshi J , Klenk HD , Kobinger G , Kortepeter MG , Kraft CS , Kratz T , Bosa HSK , Lado M , Lamontagne F , Lane HC , Lobel L , Lutwama J , Lyon GM 3rd , Massaquoi MBF , Massaquoi TA , Mehta AK , Makuma VM , Murthy S , Musoke TS , Muyembe-Tamfum JJ , Nakyeyune P , Nanclares C , Nanyunja M , Nsio-Mbeta J , O'Dempsey T , Paweska JT , Peters CJ , Piot P , Rapp C , Renaud B , Ribner B , Sabeti PC , Schieffelin JS , Slenczka W , Soka MJ , Sprecher A , Strong J , Swanepoel R , Uyeki TM , van Herp M , Vetter P , Wohl DA , Wolf T , Wolz A , Wurie AH , Yoti Z . Nat Rev Microbiol 2019 17 (5) 261-263 The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision. |
Urinary biomarkers of polycyclic aromatic hydrocarbons in pre- and peri-pubertal girls in Northern California: Predictors of exposure and temporal variability
Dobraca D , Lum R , Sjodin A , Calafat AM , Laurent CA , Kushi LH , Windham GC . Environ Res 2018 165 46-54 BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California. METHODS: Urinary concentrations of ten PAH metabolites and cotinine were quantified in 431 girls age 6-8 years at baseline. Characteristics obtained from parental interview, physical exam, and linked traffic data were examined as predictors of PAH metabolite concentrations using multivariable linear regression. A subset of girls (n = 100) had repeat measures of PAH metabolites in the second and fourth years of the study. We calculated the intraclass correlation coefficient (ICC), Spearman correlation coefficients, and how well the quartile ranking by a single measurement represented the four-year average PAH biomarker concentration. RESULTS: Eight PAH metabolites were detected in >/= 95% of the girls. The most consistent predictors of PAH biomarker concentrations were cotinine concentration, grilled food consumption, and region of residence, with some variation by demographics and season. After adjustment, select PAH metabolite concentrations were higher for Hispanic and Asian girls, and lower among black girls; 2-naphthol concentrations were higher in girls from lower income households. Other than 1-naphthol, there was modest reproducibility over time (ICCs between 0.18 and 0.49) and the concentration from a single spot sample was able to reliably rank exposure into quartiles consistent with the multi-year average. CONCLUSIONS: These results confirm diet and environmental tobacco smoke exposure as the main sources of PAHs. Controlling for these sources, differences in concentrations still existed by race for specific PAH metabolites and by income for 2-naphthol. The modest temporal variability implies adequate exposure assignment using concentrations from a single sample to define a multi-year exposure timeframe for epidemiologic exposure-response studies. |
Sub-county life expectancy: A tool to improve community health and advance health equity
Boothe VL , Fierro LA , Laurent A , Shih M . Prev Chronic Dis 2018 15 E11 Compared with people in other developed countries, Americans live shorter lives, have more disease and disability, and lag on most population health measures. Recent research suggests that this poor comparative performance is primarily driven by profound local place-based disparities. Several initiatives successfully used sub-county life expectancy estimates to identify geographic disparities, generate widespread interest, and catalyze multisector actions. To explore the feasibility of scaling these efforts, the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists initiated a multiphase project - the Sub-County Assessment of Life Expectancy. Phase I participants reviewed the literature, assessed and identified appropriate tools, calculated locally relevant estimates, and developed methodological guidance. Phase I results suggest that most state and local health departments will be able to calculate actionable sub-county life expectancy estimates despite varying resources, expertise, and population sizes, densities, and geographies. To accelerate widespread scaling, we describe several successful case examples, identify user-friendly validated tools, and provide practical tips that resulted from lessons learned. |
Comparative evaluation of anopheline sampling methods in three localities in Indonesia
St Laurent B , Sukowati S , Burton TA , Bretz D , Zio M , Firman S , Sumardi , Sudibyo H , Safitri A , Suwito , Asih PB , Kosasih S , Shinta , Hawley WA , Burkot TR , Collins FH , Syafruddin D , Lobo NF . Malar J 2018 17 (1) 13 BACKGROUND: The effectiveness of vector control efforts can vary based on the interventions used and local mosquito behaviour and adaptability. In many settings, biting patterns of Anopheles mosquitoes can shift in response to interventions targeting indoor-biting mosquitoes, often resulting in higher proportions of mosquitoes feeding outside or at times when people are not protected. These behaviourally resistant mosquitoes have been shown to sustain residual malaria transmission and limit control efforts. Therefore, it is important to accurately sample mosquitoes to understand their behaviour. METHODS: A variety of traps were evaluated in three geographically diverse sites in malaria-endemic Indonesia to investigate local mosquito feeding behaviour and determine effective traps for surveillance. RESULTS: Eight traps were evaluated in three sites: Canti village, Lampung, Kaliharjo village, Purworejo, and Saketa village, Halmahera, Indonesia, including the gold standard human landing collection (HLC) and a variety of traps targeting host-seeking and resting mosquitoes both indoors and outdoors. Trapping, using indoor and outdoor HLC, the Ifakara tent trap C, goat and human-occupied tents, resting pots and boxes, and CDC miniature light traps was conducted for 16 nights in two sites and 8 nights in a third site, using a Latin square design. Trap efficacy varied by site, with outdoor HLC yielding the highest catch rates in Canti and Kaliharjo and a goat-baited tent trap proving most effective in Saketa. In Canti village, anthropophilic Anopheles sundaicus were caught indoors and outdoors using HLCs, peaking in the early morning. In Kaliharjo, a variety of mosquitoes were caught, mostly outdoors throughout the night. HLC was ineffective in Saketa, the only site where a goat-baited tent trap was tested. This trap was effective in catching zoophilic vectors outdoors before midnight. CONCLUSIONS: Different trapping methods were suitable for different species, likely reflecting differences in behaviour among species. The three villages, each located on a different island in the Indonesian archipelago, contained mosquito populations with unique behaviours. These data suggest that the effectiveness of specific vector monitoring and control measures may vary by location. |
An Assessment of Different Genomic Approaches for Inferring Phylogeny of Listeria monocytogenes.
Henri C , Leekitcharoenphon P , Carleton HA , Radomski N , Kaas RS , Mariet JF , Felten A , Aarestrup FM , Gerner Smidt P , Roussel S , Guillier L , Mistou MY , Hendriksen RS . Front Microbiol 2017 8 2351 Background/objectives: Whole genome sequencing (WGS) has proven to be a powerful subtyping tool for foodborne pathogenic bacteria like L. monocytogenes. The interests of genome-scale analysis for national surveillance, outbreak detection or source tracking has been largely documented. The genomic data however can be exploited with many different bioinformatics methods like single nucleotide polymorphism (SNP), core-genome multi locus sequence typing (cgMLST), whole-genome multi locus sequence typing (wgMLST) or multi locus predicted protein sequence typing (MLPPST) on either core-genome (cgMLPPST) or pan-genome (wgMLPPST). Currently, there are little comparisons studies of these different analytical approaches. Our objective was to assess and compare different genomic methods that can be implemented in order to cluster isolates of L. monocytogenes. Methods: The clustering methods were evaluated on a collection of 207 L. monocytogenes genomes of food origin representative of the genetic diversity of the Anses collection. The trees were then compared using robust statistical analyses. Results: The backward comparability between conventional typing methods and genomic methods revealed a near-perfect concordance. The importance of selecting a proper reference when calling SNPs was highlighted, although distances between strains remained identical. The analysis also revealed that the topology of the phylogenetic trees between wgMLST and cgMLST were remarkably similar. The comparison between SNP and cgMLST or SNP and wgMLST approaches showed that the topologies of phylogenic trees were statistically similar with an almost equivalent clustering. Conclusion: Our study revealed high concordance between wgMLST, cgMLST, and SNP approaches which are all suitable for typing of L. monocytogenes. The comparable clustering is an important observation considering that the two approaches have been variously implemented among reference laboratories. |
Carbapenemase-Producing Organisms: A Global Scourge!
Bonomo RA , Burd EM , Conly J , Limbago BM , Poirel L , Segre JA , Westblade LF . Clin Infect Dis 2017 66 (8) 1290-1297 The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in health care environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort is needed to contain the risk of infection. Central to the treatment and control of Carbapenemase-producing organisms (CPO) are phenotypic- (growth-/biochemical-dependent) and nucleic acid-based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPO with emphasis on their epidemiology, detection, treatment, and control. |
Host attraction and biting behaviour of Anopheles mosquitoes in South Halmahera, Indonesia
St Laurent B , Burton TA , Zubaidah S , Miller HC , Asih PB , Baharuddin A , Kosasih S , Shinta , Firman S , Hawley WA , Burkot TR , Syafruddin D , Sukowati S , Collins FH , Lobo NF . Malar J 2017 16 (1) 310 BACKGROUND: Indonesia is home to a variety of malaria vectors whose specific bionomic traits remain largely uncharacterized. Species-specific behaviours, such as host feeding preferences, impact the dynamics of malaria transmission and the effectiveness of vector control interventions. METHODS: To examine species-specific host attraction and feeding behaviours, a Latin square design was used to compare Anopheles mosquitoes attracted to human, cow, and goat-baited tents. Anopheles mosquitoes were collected hourly from the inside walls of each baited tent. Species were morphologically and then molecularly identified using rDNA ITS2 sequences. The head and thorax of individual specimens were analysed for Plasmodium DNA using PCR. Bloodmeals were identified using a multiplex PCR. RESULTS: A total of 1024, 137, and 74 Anopheles were collected over 12 nights in cow, goat, and human-baited tents, respectively. The species were identified as Anopheles kochi, Anopheles farauti s.s., Anopheles hackeri, Anopheles hinesorum, Anopheles indefinitus, Anopheles punctulatus, Anopheles tessellatus, Anopheles vagus, and Anopheles vanus, many of which are known to transmit human malaria. Molecular analysis of blood meals revealed a high level of feeding on multiple host species in a single night. Anopheles kochi, An. indefinitus, and An. vanus were infected with Plasmodium vivax at rates comparable to primary malaria vectors. CONCLUSIONS: The species distributions of Anopheles mosquitoes attracted to human, goat, and cow hosts were similar. Eight of nine sporozoite positive samples were captured with animal-baited traps, indicating that even predominantly zoophilic mosquitoes may be contributing to malaria transmission. Multiple host feeding and flexibility in blood feeding behaviour have important implications for malaria transmission, malaria control, and the effectiveness of intervention and monitoring methods, particularly those that target human-feeding vectors. |
Molecular characterization reveals diverse and unknown malaria vectors in the western Kenyan highlands
St Laurent B , Cooke M , Krishnankutty SM , Asih P , Mueller JD , Kahindi S , Ayoma E , Oriango RM , Thumloup J , Drakeley C , Cox J , Collins FH , Lobo NF , Stevenson JC . Am J Trop Med Hyg 2016 94 (2) 327-35 The success of mosquito-based malaria control is dependent upon susceptible bionomic traits in local malaria vectors. It is crucial to have accurate and reliable methods to determine mosquito species composition in areas subject to malaria. An unexpectedly diverse set of Anopheles species was collected in the western Kenyan highlands, including unidentified and potentially new species carrying the malaria parasite Plasmodium falciparum. This study identified 2,340 anopheline specimens using both ribosomal DNA internal transcribed spacer region 2 and mitochondrial DNA cytochrome oxidase subunit 1 loci. Sixteen distinct sequence groups were identified. Of these, only eight could be molecularly identified through comparison to published and voucher sequences. Of the unidentified species, four were found to carry P. falciparum by circumsporozoite enzyme-linked immunosorbent assay and polymerase chain reaction, the most abundant of which had infection rates comparable to a primary vector in the area, Anopheles funestus. High-quality adult specimens of these unidentified species could not be matched to museum voucher specimens or conclusively identified using multiple keys, suggesting that they may have not been previously described. These unidentified vectors were captured outdoors. Diverse and unknown species have been incriminated in malaria transmission in the western Kenya highlands using molecular identification of unusual morphological variants of field specimens. This study demonstrates the value of using molecular methods to compliment vector identifications and highlights the need for accurate characterization of mosquito species and their associated behaviors for effective malaria control. |
Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013.
Rith S , Davis CT , Duong V , Sar B , Horm SV , Chin S , Ly S , Laurent D , Richner B , Oboho I , Jang Y , Davis W , Thor S , Balish A , Iuliano AD , Sorn S , Holl D , Sok T , Seng H , Tarantola A , Tsuyuoka R , Parry A , Chea N , Allal L , Kitsutani P , Warren D , Prouty M , Horwood P , Widdowson MA , Lindstrom S , Villanueva J , Donis R , Cox N , Buchy P . J Virol 2014 88 (23) 13897-909 Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to absence of the mutations in poultry/environmental samples, suggested the mutations occurred during human infection and did not transmit further. |
Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011
Chea N , Yi S , Rith S , Seng H , Ieng V , Penh C , Mardy S , Laurent D , Richner B , Sok T , Ly S , Kitsutani P , Asgari N , Roces M , Buchy P , Tarantola A . Euro Surveill 2014 19 (25) In February 2011, a mother and her child from Banteay Meanchey Province, Cambodia, were diagnosed, postmortem, with avian influenza A(H5N1) virus infection. A field investigation was conducted by teams from the Cambodian Ministry of Health, the World Health Organization and the Institut Pasteur in Cambodia. Nasopharyngeal, throat and serum specimens collected from 11 household or three neighbour contacts including two suspect cases tested negative by reverse transcriptase-polymerase chain reaction (RT-PCR) for A(H5N1). Follow-up sera from the 11 household contacts also tested negative for A(H5N1) antibodies. Twenty-six HCW who were exposed to the cases without taking adequate personal protective measures self-monitored and none developed symptoms within the two following weeks. An unknown number of passengers travelling with the cases on a minibus while they were symptomatic could not be traced but no clusters of severe respiratory illnesses were detected through the Cambodian surveillance systems in the two weeks after that. The likely cause of the fatal infection in the mother and the child was common-source exposure in Preah Sdach District, Prey Veng Province. Human-to-human transmission of A(H5N1) virus was unlikely but genetic susceptibility is suspected. Clusters of A(H5N1) virus infection should be systematically investigated to rule out any human-to-human transmission. |
Impact of unfounded vaccine safety concerns on the nationwide measles-rubella immunization campaign, Georgia, 2008
Khetsuriani N , Imnadze P , Baidoshvili L , Jabidze L , Tatishili N , Kurtsikashvili G , Lezhava T , Laurent E , Martin R . Vaccine 2010 28 (39) 6455-62 Vaccine safety fears following media reports of adverse events led to low (50.3%) coverage in a supplementary measles-rubella immunization campaign in Georgia in 2008. Review of adverse events associated with the campaign identified 432 reports (<0.1% of approximately 493,000 vaccinees) including 338 (78.2%) cases of syncope. There were no deaths. Causality assessment was performed for 79 cases perceived by providers as severe and with clinical details available. Conditions likely caused by the vaccine were identified in 13 (16.5%) cases (allergic and local reactions, thrombocytopenia). Thirty-seven (46.8%) cases had symptoms consistent with syncope or anxiety attack; 36 (97.3%) of them were initially misdiagnosed as anaphylactic shock/allergies/"postvaccinal reactions". Twenty-nine (36.7%) cases had coincidental illnesses. Safety fears were unfounded and exaggerated by media reports and providers' difficulties in recognizing syncope/anxiety attacks. Risk communication strategies to address perceived vaccine safety concerns are urgently needed to ensure that the goal of measles and rubella elimination in the European Region of the World Health Organization is met. |
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