Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 798 Records) |
Query Trace: John B[original query] |
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Prevention of zoonotic spillover: From relying on response to reducing the risk at source
Wanda M , Thomas CM , Wiku BA , Salama A , Casey BB , Pépé B , Salome AB , Natalia C , Natalia CB , Dominique FC , Abhishek C , Janice RCZ , Andrew AC , Osman D , Nitish D , Baptiste D , Elmoubasher F , George FG , David TSH , Margaret K , Marion PGK , Catherine M , John SM , Serge M , Vyacheslav S , Zhou L , Giraudoux P . PLoS Pathog 2023 19 (10) e1011504 |
Of Those We Have Lost and Those Who Have Saved So Many Others
Chorba T . Emerg Infect Dis 2022 28 (7) 1537-9 Modernism is a term ascribed to styles and transformative movements in multiple cultural spheres—philosophy, music, art, architecture, and literature. In its essence, modernism has at its core experimentation, as a term usually applied to efforts and creations of the late 19th or early 20th century, but sometimes later, characterized by intentional departures from traditional forms. | | There are many well-known examples of modernist efforts in their respective spheres and periods. In biology, Charles Darwin questioned the concept of human uniqueness with the theory of evolution. In literature, the term modernist has been applied to European and American writers who created substantive departures from tradition, as was seen in the works of Fyodor Dostoyevsky, Gustave Flaubert, James Joyce, and William Carlos Williams. In music, modernism is a term ascribed to the period 1890–1930, and postmodernism is a term sometimes accorded to phenomena with modernist qualities but occurring after 1930; however, some critics use modernism to describe a movement of rebellion that continues, dependent on the musician’s attitude rather than the musician’s moment in time. Certainly, Ella Fitzgerald, Miles Davis, Bob Dylan, John Lennon, Charles Mingus, the Rolling Stones, and Neil Young created musical forms that featured modernist iconoclasm, stepping well beyond the early 20th century. In art, modernism is used as a broader categorization of several novel stylistic departures including realism, postimpressionism, fauvism, cubism, dadaism, surrealism, abstract expressionism, and minimalism, each with elements of deliberate experimentation and innovation. |
Evaluation of a dried blood and plasma collection device, SampleTanker(®), for HIV type 1 drug resistance genotyping in patients receiving antiretroviral therapy.
Diallo K , Lehotzky E , Zhang J , Zhou Z , de Rivera IL , Murillo WE , Nkengasong J , Sabatier J , Zhang G , Yang C . AIDS Res Hum Retroviruses 2014 30 (1) 67-73 Whatman 903 filter paper is the only filter paper that has been used for HIV drug resistance (HIVDR) genotyping in resource-limited settings. In this study, we evaluated another dried blood specimen collection device, termed SampleTanker(®) (ST), for HIVDR genotyping. Blood specimens from 123 antiretroviral therapy (ART)-experienced patients were used to prepare ST whole blood and ST plasma specimens; they were then stored at ambient temperature for 2 or 4 weeks. The remaining plasma specimens were stored at -80°C and used as frozen plasma controls. Frozen plasma viral load (VL) was determined using the Roche Amplicor HIV-1 Monitor test, v.1.5 and 50 specimens with VL ≥3.00 log10 copies/ml were genotyped using the broadly sensitive genotyping assay. The medium VL for the 50 frozen plasma specimens with VL ≥3.00 log10 was 3.58 log10 copies/ml (IQR: 3.32-4.11) and 96.0% (48/50) of them were genotyped. Comparing to frozen plasma specimens, significantly lower genotyping rates were obtained from ST whole blood (48.98% and 42.85%) and ST plasma specimens (36.0% and 36.0%) stored at ambient temperature for 2 and 4 weeks, respectively (p<0.001). Nucleotide sequence identity and resistance profile analyses between the matched frozen plasma and ST whole blood or ST plasma specimens revealed high nucleotide sequence identities and concordant resistance profiles (98.1% and 99.0%, and 96.6% and 98.9%, respectively). Our results indicate that with the current design, the ST may not be the ideal dried blood specimen collection device for HIVDR monitoring for ART patients in resource-limited settings. |
Phenylketonuria Scientific Review Conference: state of the science and future research needs.
Camp KM , Parisi MA , Acosta PB , Berry GT , Bilder DA , Blau N , Bodamer OA , Brosco JP , Brown CS , Burlina AB , Burton BK , Chang CS , Coates PM , Cunningham AC , Dobrowolski SF , Ferguson JH , Franklin TD , Frazier DM , Grange DK , Greene CL , Groft SC , Harding CO , Howell RR , Huntington KL , Hyatt-Knorr HD , Jevaji IP , Levy HL , Lichter-Konecki U , Lindegren ML , Lloyd-Puryear MA , Matalon K , MacDonald A , McPheeters ML , Mitchell JJ , Mofidi S , Moseley KD , Mueller CM , Mulberg AE , Nerurkar LS , Ogata BN , Pariser AR , Prasad S , Pridjian G , Rasmussen SA , Reddy UM , Rohr FJ , Singh RH , Sirrs SM , Stremer SE , Tagle DA , Thompson SM , Urv TK , Utz JR , van Spronsen F , Vockley J , Waisbren SE , Weglicki LS , White DA , Whitley CB , Wilfond BS , Yannicelli S , Young JM . Mol Genet Metab 2014 112 (2) 87-122 New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. |
Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition.
Pop M , Walker AW , Paulson J , Lindsay B , Antonio M , Hossain MA , Oundo J , Tamboura B , Mai V , Astrovskaya I , Corrada Bravo H , Rance R , Stares M , Levine MM , Panchalingam S , Kotloff K , Ikumapayi UN , Ebruke C , Adeyemi M , Ahmed D , Ahmed F , Alam MT , Amin R , Siddiqui S , Ochieng JB , Ouma E , Juma J , Mailu E , Omore R , Morris JG , Breiman RF , Saha D , Parkhill J , Nataro JP , Stine OC . Genome Biol 2014 15 (6) R76 BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques. |
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. |
Coordinated evolution among hepatitis C virus genomic sites is coupled to host factors and resistance to interferon.
Lara J , Tavis JE , Donlin MJ , Lee WM , Yuan HJ , Pearlman BL , Vaughan G , Forbi JC , Xia GL , Khudyakov YE . In Silico Biol 2011 11 213-24 Machine-learning methods in the form of Bayesian networks (BN), linear projection (LP) and self-organizing tree (SOT) models were used to explore association among polymorphic sites within the HVR1 and NS5a regions of the HCV genome, host demographic factors (ethnicity, gender and age) and response to the combined interferon (IFN) and ribavirin (RBV) therapy. The BN models predicted therapy outcomes, gender and ethnicity with accuracy of 90%, 90% and 88.9%, respectively. The LP and SOT models strongly confirmed associations of the HVR1 and NS5A structures with response to therapy and demographic host factors identified by BN. The data indicate host specificity of HCV evolution and suggest the application of these models to predict outcomes of IFN/RBV therapy. |
Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru.
Akinyi S , Hayden T , Gamboa D , Torres K , Bendezu J , Abdallah JF , Griffing SM , Quezada WM , Arrospide N , De Oliveira AM , Lucas C , Magill AJ , Bacon DJ , Barnwell JW , Udhayakumar V . Sci Rep 2013 3 2797 The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. |
Expression of non-structural-1A binding protein in lung epithelial cells is modulated by miRNA-548an on exposure to influenza A virus.
Othumpangat S , Noti JD , Blachere FM , Beezhold DH . Virology 2013 447 84-94 Understanding the host response to influenza A virus infection is essential for developing intervention approaches. We show that infection of human alveolar epithelial cells and human bronchial epithelial cells with influenza A for 3h resulted in down-regulation of host hsa-miRNA-548an (miRNA-548an) which triggered the overexpression of influenza non-structural-1A binding protein (IVNS1ABP, herein referred to as NS1ABP). Reduced NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an mimic or increased NS1ABP mRNA and NS1ABP protein expression after transfection of miRNA-548an inhibitor provided evidence that miRNA-548an is involved in the regulation of NS1ABP. Transfection of cells with inhibitor led to reduced apoptosis of infected cells while transfection of mimic led to increased apoptosis and reduced influenza copy number suggesting that NS1ABP has a role in viral maintenance. Thus, miRNA-548an may be an important target in controlling the early stage infection of influenza A. |
Estimates of congenital cytomegalovirus-attributable infant mortality in high-income countries: A review
Grosse SD , Fleming P , Pesch MH , Rawlinson WD . Rev Med Virol 2024 34 (1) e2502 As many as 5%–10% of infants with symptomatic congenital cytomegalovirus (cCMV) disease, or 0.4%–0.8% of all liveborn infants with cCMV infection, die in early infancy in high-income countries. However, estimates are uncertain due to several potential biases that can result from data limitations and study designs. First, infants with cCMV infections who die prior to diagnosis, which usually occurs at 1–4 weeks after birth, may be excluded from both the count of deaths and the denominator of cCMV births, resulting in left truncation and immortal time biases. These ‘biases’ are features of the data and do not reflect bias on the part of researchers, but understanding the potential existence of threats to validity can help with interpretation of findings. Left truncation of infant deaths occurring prior to diagnosis of cCMV can result in understatement of the burden of infant deaths due to cCMV. Conversely, overestimation of infant deaths associated with symptomatic cCMV may occur in clinical case series owing to greater representation of relatively severely affected infants owing to ascertainment and referral biases. In this review, we summarise the characteristics of 26 studies that reported estimates of cCMV-associated infant deaths, including potential biases or limitations to which those estimates may have been subject. We discuss study designs whose implementation might generate improved estimates of infant deaths attributable to cCMV. More complete estimates of the overall public health impact of cCMV could inform current and future screening, prevention, and vaccine research. © 2024 John Wiley & Sons Ltd. |
Post-discharge malaria chemoprevention in children admitted with severe anaemia in malaria-endemic settings in Africa: a systematic review and individual patient data meta-analysis of randomised controlled trials
Phiri KS , Khairallah C , Kwambai TK , Bojang K , Dhabangi A , Opoka R , Idro R , Stepniewska K , van Hensbroek MB , John CC , Robberstad B , Greenwood B , Kuile FOT . Lancet Glob Health 2024 12 (1) e33-e44 BACKGROUND: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia. METHODS: This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791. FINDINGS: Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I(2)=0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias. INTERPRETATION: In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity. FUNDING: The Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network. |
Endophthalmitis, cutaneous nodules, and brain lesions in stem cell transplant recipient
Axell-House DB , Nagarajan P , Bhatti MM , Mehta RS , Roy S , Ali IKM , John TM . Clin Infect Dis 2023 77 (8) 1212-1215 A 46-year-old man with relapsed acute myeloid leukemia underwent his second matched related donor stem cell transplant (SCT), after fludarabine and melphalan conditioning followed by post-transplant cyclophosphamide. He engrafted on day +20. On day +27, he developed fever, sinusitis, left eyelid swelling, and right eye subconjunctival swelling (Figure 1A). He required an urgent right vitrectomy for endophthalmitis. Seven days later, he developed skin nodules on his upper and lower extremities which progressively enlarged and became more diffuse (Figure 1Band 1C). Laboratory tests showed leukopenia (white blood cell count 3.1 × 109/L), anemia (Hb 7.2 g/dL), and severe thrombocytopenia (25 × 109/L) with normal electrolytes, and normal renal and hepatic function. Blood, urine, and sputum cultures were no growth, and infectious serologies, nucleic acid, and antigen tests were negative, including for human immunodeficiency virus, syphilis, Toxoplasma, tuberculosis, cytomegalovirus, and Strongyloides. Nasal endoscopy did not demonstrate necrosis of sinus tissue, and sinus swab cultures did not grow any organisms of clinical significance. Wide excisional skin biopsies of skin lesions demonstrated a lymphohistiocytic infiltrate and panniculitis (Figure 2A) and circular structures (Figure 2B). Vitrectomy was performed for endophthalmitis, and vitreous fluid cultures had no growth. Positron emission tomography (PET) demonstrated diffuse subcutaneous foci most numerous of the lower extremities, and a left occipitotemporal focus (Figure 3A). Shortly thereafter, he developed acute encephalopathy, drowsiness, and rhythmic movements of his right arm concerning for seizures. Brain magnetic resonance imaging (MRI) demonstrated abnormalities of the left frontal gyrus, occipital lobe, parieto-occipital sulcus, and cerebellum, concerning for embolic strokes (Figure 3B). He continued to have fever and progression of skin lesions despite treatment with meropenem, vancomycin, minocycline, and amphotericin. What is the likely diagnosis? |
Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Carey ME , Dyson ZA , Ingle DJ , Amir A , Aworh MK , Chattaway MA , Chew KL , Crump JA , Feasey NA , Howden BP , Keddy KH , Maes M , Parry CM , Van Puyvelde S , Webb HE , Afolayan AO , Alexander AP , Anandan S , Andrews JR , Ashton PM , Basnyat B , Bavdekar A , Bogoch II , Clemens JD , da Silva KE , De A , de Ligt J , Diaz Guevara PL , Dolecek C , Dutta S , Ehlers MM , Francois Watkins L , Garrett DO , Godbole G , Gordon MA , Greenhill AR , Griffin C , Gupta M , Hendriksen RS , Heyderman RS , Hooda Y , Hormazabal JC , Ikhimiukor OO , Iqbal J , Jacob JJ , Jenkins C , Jinka DR , John J , Kang G , Kanteh A , Kapil A , Karkey A , Kariuki S , Kingsley RA , Koshy RM , Lauer AC , Levine MM , Lingegowda RK , Luby SP , Mackenzie GA , Mashe T , Msefula C , Mutreja A , Nagaraj G , Nagaraj S , Nair S , Naseri TK , Nimarota-Brown S , Njamkepo E , Okeke IN , Perumal SPB , Pollard AJ , Pragasam AK , Qadri F , Qamar FN , Rahman SIA , Rambocus SD , Rasko DA , Ray P , Robins-Browne R , Rongsen-Chandola T , Rutanga JP , Saha SK , Saha S , Saigal K , Sajib MSI , Seidman JC , Shakya J , Shamanna V , Shastri J , Shrestha R , Sia S , Sikorski MJ , Singh A , Smith AM , Tagg KA , Tamrakar D , Tanmoy AM , Thomas M , Thomas MS , Thomsen R , Thomson NR , Tupua S , Vaidya K , Valcanis M , Veeraraghavan B , Weill FX , Wright J , Dougan G , Argimón S , Keane JA , Aanensen DM , Baker S , Holt KE . Elife 2023 12 BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng |
Inferring time of infection from field data using dynamic models of antibody decay
Borremans B , Mummah RO , Guglielmino AH , Galloway RL , Hens N , Prager KC , Lloyd-Smith JO . Methods Ecol Evol 2023 Studies of infectious disease ecology would benefit greatly from knowing when individuals were infected, but estimating this time of infection can be challenging, especially in wildlife. Time of infection can be estimated from various types of data, with antibody-level data being one of the most promising sources of information. The use of antibody levels to back-calculate infection time requires the development of a host-pathogen system-specific model of antibody dynamics, and a leading challenge in such quantitative serology approaches is how to model antibody dynamics in the absence of experimental infection data. We present a way to model antibody dynamics in a Bayesian framework that facilitates the incorporation of all available information about potential infection times and apply the model to estimate infection times of Channel Island foxes infected with Leptospira interrogans. Using simulated data, we show that the approach works well across a broad range of parameter settings and can lead to major improvements in infection time estimates that depend on system characteristics such as antibody decay rate and variation in peak antibody levels after exposure. When applied to field data we saw reductions up to 83% in the window of possible infection times. The method substantially simplifies the challenge of modelling antibody dynamics in the absence of individuals with known infection times, opens up new opportunities in wildlife disease ecology and can even be applied to cross-sectional data once the model is trained. © 2023 The Authors. Methods in Ecology and Evolution published by John Wiley & Sons Ltd on behalf of British Ecological Society. |
Cause-specific student absenteeism monitoring in K-12 schools for detection of increased influenza activity in the surrounding community - Dane County, Wisconsin, 2014-2020 (preprint)
Temte JL , Barlow S , Goss M , Temte E , Schemmel A , Bell C , Reisdorf E , Shult P , Wedig M , Haupt T , Conway JH , Gangnon R , Uzicanin A . medRxiv 2021 2021.05.26.21257819 Background Schools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.Materials and Methods Between September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.Findings Influenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.Discussion Surveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.Competing Interest StatementDr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests.Funding StatementThis study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.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:All components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education and Social/Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December 5, 2013, with additional approvals as the protocol expanded and modified). The study is in full compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), FERPA, and all other federally mandated human subjects regulations. The US Office of Management and Budget has approved all forms used in this study.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 ClinicalTrials.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.YesThe datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request. |
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit (preprint)
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . medRxiv 2020 2020.12.11.20236919 Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method.Methods MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 µM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods.Findings Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal.Interpretation Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.Competing Interest StatementAuthors Thomas S. Lendvay, James Chen are Co-Founders and equity owners of Singletto, Inc. (Seattle, WA, USA) Authors Yi Cui and Steven Chu are Co-Founders and equity owners of 4C Air, Inc. (Sunnyvale, CA)Funding StatementThis study was funded by Open Philanthropy; Amazon Inc./University of Washington Catalyst Award; University of Liege (Belgium) and the Walloon Region, Belgium; Li Ka Shing Institute; Alberta Health Services; and an Anonymous donor to the University of Washington, Department of Urology.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:Stanford University and Alberta Health Services/University of Calgary were exempt from IRB as the human fit testing was considered Quality Improvement. ERB for clinical specimen use: A clinical saliva specimen with a SARS-CoV-2 was provided by Dr. John Conly from Calgary, Alberta with Calgary ERB approval (ID# Pro00099761).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 inte ventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.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.YesData will be freely shared post publication on reasonable request by contacting the corresponding author of the study. |
The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS): Rationale, Objectives, and Design (preprint)
Temte JL , Barlow S , Goss M , Temte E , Schemmel A , Maerz B , Bell C , Comp L , Arnold M , Breunig K , Clifford S , Reisdorf E , Shult P , Wedig M , Haupt T , Conway J , Gangnon R , Fowlkes A , Uzicanin A . medRxiv 2021 2021.02.01.21250878 Background Influenza viruses pose significant disease burdens through annual seasonal outbreaks and unpredictable pandemics. Existing influenza surveillance programs have relied heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness–specific student absenteeism (a-ILI) in pre-kindergarten through grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.Methods Starting in September 2014, ORCHARDS combined automated reporting of daily absenteeism within 6 schools and home visits to school children with acute respiratory infections (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing, long-standing, and highly effective influenza surveillance program, based on MAI at 5 primary care clinics in the same geographical area.Results Over the first 5 years, a-ILI occurred on 6,634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of the 1,728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Influenza (p<0.001) and adenovirus (P=0.004) were significantly associated with a-ILI.Conclusion ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Initial findings suggest the study design is succeeding in collecting appropriate data to achieve study objectives.Competing Interest StatementDr. Jonathan Temte has received financial and material support from Quidel Corporation. Dr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests.Funding StatementDr. John Tamerius and Quidel Corporation have generously supplied RIDT analyzers and tests. This study has been supported by CDC through the cooperative agreement # 5U01CK000542-02-00. The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. 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:All components of this proposed study were reviewed and approved by the Human Subjects Committees of the Education Research IRB - Social and Behavioral Sciences IRB (initial approval on September 4, 2013) and the University of Wisconsin Health Sciences-IRB (initial approval on December 5, 2013, with additional approvals as the protocol expanded and modified). The study is in full compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA), FERPA, and all other federally mandated human subjects regulations. The US Office of Management and Budget has approved all forms used in this study.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 ClinicalTrials.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 s atement 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.YesThe datasets generated and/or analyzed during the current study are not publicly available because the study is ongoing, but may be available from the corresponding author on reasonable request.4k4-year-old pre-kindergartena-Iabsenteeism due to illnessa-ILIabsenteeism due to influenza-like illnessa-TOTall-cause absenteeismARIacute respiratory infectionCDCCenters for Disease Control and PreventionCoVcoefficient of variationFERPAFamily Educational Rights and Privacy ActFluinfluenzaFDAFood and Drug AdministrationHIPPAHealth Insurance Portability and Accountability ActILIinfluenza-like illnessITinformation technologyIRBinstitutional review boardMAImedically attended influenzaNPnasopharyngealORCHARDSOregon Child Absenteeism Due to Respiratory Disease StudyOSDOregon School DistrictOPoropharyngealPCRpolymerase chain reactionRIDTrapid influenza diagnostic testRedCapResearch Electronic Data CaptureRPPrespiratory pathogen panelR/Erhinovirus/enterovirusRPhuman RNAse PSISschool information systemW-IISPWisconsin Influenza Incidence Surveillance ProjectWIRWisconsin Immunization RegistryWSLHWisconsin State Laboratory of HygieneVTMviral transport medium |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13 (preprint)
Arizti-Sanz J , Bradley AD , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TSF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , Happi CT , Johnson J , Sabeti PC , Myhrvold C . medRxiv 2021 02 The COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location. 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. |
Early detection of SARS-CoV-2 variants using traveler-based genomic surveillance at four US airports, September 2021- January 2022 (preprint)
Wegrzyn RD , Appiah GD , Morfino R , Milford SR , Walker AT , Ernst ET , Darrow WW , Li SL , Robison K , MacCannell D , Dai D , Girinathan BP , Hicks AL , Cosca B , Woronoff G , Plocik AM , Simen BB , Moriarty L , Guagliardo SAJ , Cetron MS , Friedman CR . medRxiv 2022 22 Background Despite layered mitigation measures, international travel during the COVID-19 pandemic continues to facilitate global spread of SARS-CoV-2, including novel variants of concern (VOCs). On November 26, 2021, B.1.1.529 (Omicron) was designated as a VOC by the World Health Organization [1]. On December 6, 2021, as part of measures to reduce the introduction and spread of Omicron, the requirement for a negative SARS-CoV-2 test taken before air travel to the United States was shortened from three days to one day pre-departure [1]. Although SARS-CoV-2 genomic sequencing has increased significantly during the pandemic [2], there is still a gap in early detection of emerging variants among arriving travelers. In September 2021, the Centers for Disease Control and Prevention (CDC), in collaboration with private partners, implemented a voluntary SARS-CoV-2 genomic surveillance pilot program. Initially we enrolled arriving air travelers from India. On November 28, we expanded the program to include travelers arriving from countries with high travel volumes, including those where Omicron was first detected. Methods Design, Setting, and Participants During September 29-November 27, 2021, the surveillance program included travelers arriving on seven direct flights from India at three international airports: John F. Kennedy, New York (September 29), Newark Liberty, New Jersey (October 4), and San Francisco, California (October 12). During November 28-January 23, Hartsfield-Jackson Atlanta International Airport, Georgia was added, and participation was offered to travelers from South Africa, Nigeria, the United Kingdom, France, Germany, and Brazil, arriving on approximately 50 flights per day. Participants were 18 years or older, provided informed consent, and completed demographic, clinical, and travel history questions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Life expectancy by county, race, and ethnicity in the USA, 2000-19: a systematic analysis of health disparities
GBD US Health Disparities Collaborators , Dwyer-Lindgren Laura , Kendrick Parkes , Kelly Yekaterina O , Sylte Dillon O , Schmidt Chris , Blacker Brigette F , Daoud Farah , Abdi Amal A , Baumann Mathew , Mouhanna Farah , Kahn Ethan , Hay Simon I , Mensah George A , Nápoles Anna M , Pérez-Stable Eliseo J , Shiels Meredith , Freedman Neal , Arias Elizabeth , George Stephanie A , Murray David M , Phillips John Wr , Spittel Michael L , Murray Christopher Jl , Mokdad Ali H . Lancet 2022 400 (10345) 25-38 BACKGROUND: There are large and persistent disparities in life expectancy among racial-ethnic groups in the USA, but the extent to which these patterns vary geographically on a local scale is not well understood. This analysis estimated life expectancy for five racial-ethnic groups, in 3110 US counties over 20 years, to describe spatial-temporal variations in life expectancy and disparities between racial-ethnic groups. METHODS: We applied novel small-area estimation models to death registration data from the US National Vital Statistics System and population data from the US National Center for Health Statistics to estimate annual sex-specific and age-specific mortality rates stratified by county and racial-ethnic group (non-Latino and non-Hispanic White [White], non-Latino and non-Hispanic Black [Black], non-Latino and non-Hispanic American Indian or Alaska Native [AIAN], non-Latino and non-Hispanic Asian or Pacific Islander [API], and Latino or Hispanic [Latino]) from 2000 to 2019. We adjusted these mortality rates to correct for misreporting of race and ethnicity on death certificates and then constructed abridged life tables to estimate life expectancy at birth. FINDINGS: Between 2000 and 2019, trends in life expectancy differed among racial-ethnic groups and among counties. Nationally, there was an increase in life expectancy for people who were Black (change 3·9 years [95% uncertainty interval 3·8 to 4·0]; life expectancy in 2019 75·3 years [75·2 to 75·4]), API (2·9 years [2·7 to 3·0]; 85·7 years [85·3 to 86·0]), Latino (2·7 years [2·6 to 2·8]; 82·2 years [82·0 to 82·5]), and White (1·7 years [1·6 to 1·7]; 78·9 years [78·9 to 79·0]), but remained the same for the AIAN population (0·0 years [-0·3 to 0·4]; 73·1 years [71·5 to 74·8]). At the national level, the negative difference in life expectancy for the Black population compared with the White population decreased during this period, whereas the negative difference for the AIAN population compared with the White population increased; in both cases, these patterns were widespread among counties. The positive difference in life expectancy for the API and Latino populations compared with the White population increased at the national level from 2000 to 2019; however, this difference declined in a sizeable minority of counties (615 [42·0%] of 1465 counties) for the Latino population and in most counties (401 [60·2%] of 666 counties) for the API population. For all racial-ethnic groups, improvements in life expectancy were more widespread across counties and larger from 2000 to 2010 than from 2010 to 2019. INTERPRETATION: Disparities in life expectancy among racial-ethnic groups are widespread and enduring. Local-level data are crucial to address the root causes of poor health and early death among disadvantaged groups in the USA, eliminate health disparities, and increase longevity for all. FUNDING: National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Science Research, US National Institutes of Health. |
Cost of Tuberculosis Therapy Directly Observed on Video for Health Departments and Patients in New York City; San Francisco, California; and Rhode Island (2017-2018)
Beeler Asay GR , Lam CK , Stewart B , Mangan JM , Romo L , Marks SM , Morris SB , Gummo CL , Keh CE , Hill AN , Thomas A , Macaraig M , St John K , JAmpie T , Chuck C , Burzynski J . Am J Public Health 2020 110 (11) 1696-1703 Objectives. To assess costs of video and traditional in-person directly observed therapy (DOT) for tuberculosis (TB) treatment to health departments and patients in New York City, Rhode Island, and San Francisco, California.Methods. We collected health department costs for video DOT (VDOT; live and recorded), and in-person DOT (field- and clinic-based). Time-motion surveys estimated provider time and cost. A separate survey collected patient costs. We used a regression model to estimate cost by DOT type.Results. Between August 2017 and June 2018, 343 DOT sessions were captured from 225 patients; 87 completed a survey. Patient costs were lowest for VDOT live ($1.01) and highest for clinic DOT ($34.53). The societal (health department + patient) costs of VDOT live and recorded ($6.65 and $12.64, respectively) were less than field and clinic DOT ($21.40 and $46.11, respectively). VDOT recorded health department cost was not statistically different from field DOT cost in Rhode Island.Conclusions. Among the 4 different modalities, both types of VDOT were associated with lower societal costs when compared with traditional forms of DOT.Public Health Implications. VDOT was associated with lower costs from the societal perspective and may reduce public health costs when TB incidence is high. |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Innovations in public health surveillance: updates from a forum convened by the WHO Hub for Pandemic and Epidemic Intelligence, 2 and 3 February 2022.
Morgan Oliver , Redies Isabel , Beatriz Leiva Rioja Zoila , Brownstein John , George Dylan , Golding Josie , Hanefeld Johanna , Horby Peter , Lee Christopher , Mikhailov Danil , Philip Wolfgang , Scarpino Samuel , Kifle Tessema Sofonias , Ihekweazu Chikwe . Euro Surveill 2022 27 (15) In the 2 years since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) there has been an unprecedented collective effort from the academic, public, and private sectors to advance surveillance for pandemic preparedness and response. The coronavirus disease (COVID-19) pandemic has created momentum that will define the future of public health intelligence. On 2 and 3 February 2022, the World Health Organization (WHO) Hub for Pandemic and Epidemic Intelligence convened a meeting of a small group of surveillance innovators to share insights and approaches about their initiatives and future directions. The meeting served as an opportunity for participants to share updates about their work, to explore potential for collaboration, exchange ideas, cross-fertilise our work and discuss challenges in the field of surveillance. Although the group of attendees was not geographically representative of the global surveillance community, the meeting was the first in a planned series of exchanges convened by the WHO Pandemic Hub that will generate dialogue among global thought leaders and new voices in the surveillance community. In this first convening we discussed several themes, including what is meaningful collaboration for success; how to bring the public back into public health; what are individual-centred approaches; how new kinds of data have new privacy concerns; how government structures affect the functioning of surveillance systems; how to inform the decisionmaking process; cross-scaling and down-scaling tools and technologies; investing in human talent and future practitioners; and achieving sustainability into surveillance. In this meeting report, we summarise the discussions on innovations in public health surveillance and provide a list with references and links to the organisations and initiatives represented at the meeting. |
Incomplete influenza A virus genomes occur frequently but are readily complemented during localized viral spread.
Jacobs NT , Onuoha NO , Antia A , Steel J , Antia R , Lowen AC . Nat Commun 2019 10 (1) 3526 Segmentation of viral genomes into multiple RNAs creates the potential for replication of incomplete viral genomes (IVGs). Here we use a single-cell approach to quantify influenza A virus IVGs and examine their fitness implications. We find that each segment of influenza A/Panama/2007/99 (H3N2) virus has a 58% probability of being replicated in a cell infected with a single virion. Theoretical methods predict that IVGs carry high costs in a well-mixed system, as 3.6 virions are required for replication of a full genome. Spatial structure is predicted to mitigate these costs, however, and experimental manipulations of spatial structure indicate that local spread facilitates complementation. A virus entirely dependent on co-infection was used to assess relevance of IVGs in vivo. This virus grows robustly in guinea pigs, but is less infectious and does not transmit. Thus, co-infection allows IVGs to contribute to within-host spread, but complete genomes may be critical for transmission. |
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. |
Corrigendum: Whole Genome Sequencing: Bridging One-Health Surveillance of Foodborne Diseases.
Gerner-Smidt P , Besser J , Concepción-Acevedo J , Folster JP , Huffman J , Joseph LA , Kucerova Z , Nichols MC , Schwensohn CA , Tolar B . Front Public Health 2019 7 365 In the original article, there was a mistake in Figure 1 and Figure 2 as published. The graphics used are different than those originally submitted. |
Ebola Virus Disease Outbreak - Democratic Republic of the Congo, August 2018-November 2019.
Aruna A , Mbala P , Minikulu L , Mukadi D , Bulemfu D , Edidi F , Bulabula J , Tshapenda G , Nsio J , Kitenge R , Mbuyi G , Mwanzembe C , Kombe J , Lubula L , Shako JC , Mossoko M , Mulangu F , Mutombo A , Sana E , Tutu Y , Kabange L , Makengo J , Tshibinkufua F , Ahuka-Mundeke S , Muyembe JJ , Ebola Response CDC , Alarcon Walter , Bonwitt Jesse , Bugli Dante , Bustamante Nirma D , Choi Mary , Dahl Benjamin A , DeCock Kevin , Dismer Amber , Doshi Reena , Dubray Christine , Fitter David , Ghiselli Margherita , Hall Noemi , Hamida Amen Ben , McCollum Andrea M , Neatherlin John , Raghunathan Pratima L , Ravat Fatima , Reynolds Mary G , Rico Adriana , Smith Nailah , Soke Gnakub Norbert , Trudeau Aimee T , Victory Kerton R , Worrell Mary Claire . MMWR Morb Mortal Wkly Rep 2019 68 (50) 1162-1165 On August 1, 2018, the Democratic Republic of the Congo Ministry of Health (DRC MoH) declared the tenth outbreak of Ebola virus disease (Ebola) in DRC, in the North Kivu province in eastern DRC on the border with Uganda, 8 days after another Ebola outbreak was declared over in northwest Équateur province. During mid- to late-July 2018, a cluster of 26 cases of acute hemorrhagic fever, including 20 deaths, was reported in North Kivu province.* Blood specimens from six patients hospitalized in the Mabalako health zone and sent to the Institut National de Recherche Biomédicale (National Biomedical Research Institute) in Kinshasa tested positive for Ebola virus. Genetic sequencing confirmed that the outbreaks in North Kivu and Équateur provinces were unrelated. From North Kivu province, the outbreak spread north to Ituri province, and south to South Kivu province (1). On July 17, 2019, the World Health Organization designated the North Kivu and Ituri outbreak a public health emergency of international concern, based on the geographic spread of the disease to Goma, the capital of North Kivu province, and to Uganda and the challenges to implementing prevention and control measures specific to this region (2). This report describes the outbreak in the North Kivu and Ituri provinces. As of November 17, 2019, a total of 3,296 Ebola cases and 2,196 (67%) deaths were reported, making this the second largest documented outbreak after the 2014-2016 epidemic in West Africa, which resulted in 28,600 cases and 11,325 deaths.(†) Since August 2018, DRC MoH has been collaborating with partners, including the World Health Organization, the United Nations Children's Fund, the United Nations Office for the Coordination of Humanitarian Affairs, the International Organization of Migration, The Alliance for International Medical Action (ALIMA), Médecins Sans Frontières, DRC Red Cross National Society, and CDC, to control the outbreak. Enhanced communication and effective community engagement, timing of interventions during periods of relative stability, and intensive training of local residents to manage response activities with periodic supervision by national and international personnel are needed to end the outbreak. |
Screening for Covid-19 in Skilled Nursing Facilities. Reply.
Hatfield KM , Reddy SC , Jernigan JA . N Engl J Med 2020 383 (2) 192 The authors reply: We thank Calbo and colleagues for highlighting the need to better understand the role of asymptomatic shedding in transmission of SARS-CoV-2 in health care settings. Our study focused on transmission of SARS-CoV-2 from asymptomatic and presymptomatic residents in a skilled nursing facility. As we noted, health care personnel with undetected infection probably contributed to transmission in this facility, but we could not document this because we were unable to test asymptomatic health care personnel as part of this investigation owing to limited testing resources at the time. Since that investigation, the CDC has provided guidance on testing strategies in nursing homes.1 In addition, the CDC recommends universal source control in all health care settings to help prevent transmission from health care personnel with unrecognized SARS-CoV-2 infection.2 | | The data provided by Calbo et al. suggest important hypotheses about the role of patients and health care personnel with asymptomatic SARS-CoV-2 infection in ongoing transmission in acute care facilities, a setting that is distinct from the residential skilled nursing facility described in our article. Further studies may help to better quantify the benefit of active surveillance (including laboratory testing) when added to active symptom screening and universal source control in various health care settings. |
Cryptic transmission of SARS-CoV-2 in Washington State.
Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Huang ML , Nalla A , Pepper G , Reinhardt A , Xie H , Shrestha L , Nguyen TN , Adler A , Brandstetter E , Cho S , Giroux D , Han PD , Fay K , Frazar CD , Ilcisin M , Lacombe K , Lee J , Kiavand A , Richardson M , Sibley TR , Truong M , Wolf CR , Nickerson DA , Rieder MJ , Englund JA , Hadfield J , Hodcroft EB , Huddleston J , Moncla LH , Müller NF , Neher RA , Deng X , Gu W , Federman S , Chiu C , Duchin J , Gautom R , Melly G , Hiatt B , Dykema P , Lindquist S , Queen K , Tao Y , Uehara A , Tong S , MacCannell D , Armstrong GL , Baird GS , Chu HY , Shendure J , Jerome KR . medRxiv 2020 Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding. |
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