Recent publications from TDC authors

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NCBI: db=pubmed; Term=(Yansouni C[Author]) OR (Iqbal A[Author] parasitology) OR (Ndao M[Author]) OR (Ward BJ[Author]) OR (Semret M[Author]) OR (Libman M[Author]) OR (Greenaway C[author]) OR (Barkati S[Author])
Updated: 2 hours 52 min ago

Methods to reliably estimate faecal sludge quantities and qualities for the design of treatment technologies and management solutions.

Sun, 07/15/2018 - 00:04
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Methods to reliably estimate faecal sludge quantities and qualities for the design of treatment technologies and management solutions.

J Environ Manage. 2018 Jul 09;223:898-907

Authors: Strande L, Schoebitz L, Bischoff F, Ddiba D, Okello F, Englund M, Ward BJ, Niwagaba CB

Abstract
Sanitation access in urban areas of low-income countries is provided through unstandardized onsite technologies containing accumulated faecal sludge. The demand for infrastructure to manage faecal sludge is increasing, however, no reliable method exists to estimate total accumulated quantities and qualities (Q&Q) This proposed approach averages out complexities to estimate conditions at a centralized to semi-centralized scale required for management and treatment technology solutions, as opposed to previous approaches evaluating what happens in individual containments. Empirical data, demographic data, and questionnaires were used in Kampala, Uganda to estimate total faecal sludge accumulation in the city, resulting in 270 L/cap∙year for pit latrines and 280 L/cap∙year for septic tanks. Septic tank sludge was more dilute than pit latrine sludge, however, public toilet was not a distinguishing factor. Non-household sources of sludge represent a significant fraction of the total and have different characteristics than household-level sludge. Income level, water connection, black water only, solid waste, number of users, containment volume, emptying frequency, and truck size were predictors of sludge quality. Empirical relationships such as a COD:TS of 1.09 ± 0.56 could be used for more resource efficient sampling campaigns. Based on this approach, spatially available demographic, technical and environmental (SPA-DET) data and statistical relationships between parameters could be used to predict Q&Q of faecal sludge.

PMID: 30005415 [PubMed - as supplied by publisher]

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response.

Wed, 07/11/2018 - 00:04
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A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response.

Clin Vaccine Immunol. 2017 Dec;24(12):

Authors: Hodgins B, Yam KK, Winter K, Pillet S, Landry N, Ward BJ

Abstract
Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.

PMID: 29021303 [PubMed - indexed for MEDLINE]

Hepatic cytolysis and bicytopenia after 15 days of four-drug tuberculosis treatment in Senegal.

Sun, 07/01/2018 - 00:12
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Hepatic cytolysis and bicytopenia after 15 days of four-drug tuberculosis treatment in Senegal.

Med Sante Trop. 2017 Aug 01;27(3):233-234

Authors: Thiam K, Sagne JMAN, Ndiaye EHM, Cissé MF, Mbaye FBR, Touré NO, Dia Kane Y, Diatta A, Niang S, Kombila UD, Dia S, Ndao M, Ka W

Abstract
We report the case of a 31-year-old immunocompetent woman residing in Senegal, with localized microscopy-proved pulmonary tuberculosis, complicated by macrophage activation syndrome and associated with viral hepatitis B, identified due to hepatic cytolysis and a bicytopenia.

PMID: 28947398 [PubMed - indexed for MEDLINE]

Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease.

Sat, 06/30/2018 - 00:58
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Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease.

Respiration. 2018 Jun 28;:1-19

Authors: Salzer HJF, Burchard G, Cornely OA, Lange C, Rolling T, Schmiedel S, Libman M, Capone D, Le T, Dalcolmo MP, Heyckendorf J

Abstract
Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment.

PMID: 29953992 [PubMed - as supplied by publisher]

Fever in the tropics: the ultimate clinical challenge ?

Thu, 06/28/2018 - 00:44
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Fever in the tropics: the ultimate clinical challenge ?

Clin Microbiol Infect. 2018 Jun 22;:

Authors: Bottieau E, Yansouni CP

PMID: 29940346 [PubMed - as supplied by publisher]

A novel serological assay for influenza based on DiD fluorescence dequenching that is free from observer bias and potentially automatable - A proof of concept study.

Thu, 06/28/2018 - 00:44
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A novel serological assay for influenza based on DiD fluorescence dequenching that is free from observer bias and potentially automatable - A proof of concept study.

Vaccine. 2018 Jun 18;:

Authors: Makarkov AI, Patel AR, Bainov V, Ward BJ

Abstract
BACKGROUND: Serum hemagglutination inhibition (HAI) and microneutralization (MN) antibodies are often used as a correlate of protection for influenza. However, these manual assays are labor-intensive and difficult to standardize due to variability in biologic reagents used and subjective interpretation of the results.
METHODS: Sera with known HAI and MN titers were used to assess a novel test based on the inhibition of fluorescence 'dequenching'. Whole influenza virions (A/California/07/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2) and B/Brisbane/60/2008) labelled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate (DiD) were exposed to serial dilutions of serum and mixed with turkey red blood cells followed by acidification of the media (pH 5.0-5.5). The H1N1 and B/Brisbane strains were high hemagglutinating while the H3N2 strain had low hemagglutinating activity. In some experiments, labelled virions were subjected to repetitive freeze-thaw cycles prior to use in the assay.
RESULTS: In the absence of detectable HAI/MN antibodies, there were consistent and substantial increases from baseline DiD fluorescence upon acidification. Sera with known high titer HAI/MN antibodies reduced or completely prevented DiD dequenching at low dilutions with progressive increases in fluorescence at higher dilutions, which permitted a reproducible assignment of an antibody 'titer' based on baseline and acidified DiD fluorescence values. The 'titers' measured by the DiD dequenching assay were highly correlated with HAI/MN results for the H1N1 and B strains (Spearman's correlation coefficients (rs) 0.874 to 0.946, p < 10-7 to 10-35). Correlations with HAI/MN titres for the low-hemagglutinating H3N2 strain tested were lower but remained statistically significant (rs 0.547-0.551, p < 0.004). Freeze-thawing of the DiD pre-stained virus stocks had no significant impact on the results of the assay.
CONCLUSIONS: The DiD dequenching assay may be a labour-saving and more objective alternative to the classic serologies. This novel assay could theoretically be standardized across laboratories using pre-stained virions and has the potential to be fully automated.

PMID: 29929824 [PubMed - as supplied by publisher]

Underestimate of annual malaria imports to Canada.

Sat, 06/23/2018 - 00:15
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Underestimate of annual malaria imports to Canada.

Lancet Infect Dis. 2017 02;17(2):141-142

Authors: Boggild AK, McCarthy AE, Libman MD, Freedman DO, Kain KC

PMID: 28134112 [PubMed - indexed for MEDLINE]

Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma.

Thu, 06/21/2018 - 00:09
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Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma.

Front Immunol. 2018;9:1249

Authors: Restori KH, Srinivasa BT, Ward BJ, Fixman ED

Abstract
Infants are exposed to a wide range of potential pathogens in the first months of life. Although maternal antibodies acquired transplacentally protect full-term neonates from many systemic pathogens, infections at mucosal surfaces still occur with great frequency, causing significant morbidity and mortality. At least part of this elevated risk is attributable to the neonatal immune system that tends to favor T regulatory and Th2 type responses when microbes are first encountered. Early-life infection with respiratory viruses is of particular interest because such exposures can disrupt normal lung development and increase the risk of chronic respiratory conditions, such as asthma. The immunologic mechanisms that underlie neonatal host-virus interactions that contribute to the subsequent development of asthma have not yet been fully defined. The goals of this review are (1) to outline the differences between the neonatal and adult immune systems and (2) to present murine and human data that support the hypothesis that early-life interactions between the immune system and respiratory viruses can create a lung environment conducive to the development of asthma.

PMID: 29915592 [PubMed]

Protocols for the Investigation of Information Processing in Human Assessment of Fundamental Movement Skills.

Sun, 06/17/2018 - 00:57
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Protocols for the Investigation of Information Processing in Human Assessment of Fundamental Movement Skills.

J Mot Behav. 2017 Nov-Dec;49(6):593-602

Authors: Ward BJ, Thornton A, Lay B, Rosenberg M

Abstract
Fundamental movement skill (FMS) assessment remains an important tool in classifying individuals' level of FMS proficiency. The collection of FMS performances for assessment and monitoring has remained unchanged over the last few decades, but new motion capture technologies offer opportunities to automate this process. To achieve this, a greater understanding of the human process of movement skill assessment is required. The authors present the rationale and protocols of a project in which they aim to investigate the visual search patterns and information extraction employed by human assessors during FMS assessment, as well as the implementation of the Kinect system for FMS capture.

PMID: 28010182 [PubMed - indexed for MEDLINE]

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

Thu, 05/24/2018 - 00:43
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Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

BMC Infect Dis. 2017 12 29;17(1):805

Authors: Andrew MK, Shinde V, Hatchette T, Ambrose A, Boivin G, Bowie W, Chit A, Dos Santos G, ElSherif M, Green K, Haguinet F, Halperin SA, Ibarguchi B, Johnstone J, Katz K, Langley JM, LeBlanc J, Loeb M, MacKinnon-Cameron D, McCarthy A, McElhaney J, McGeer A, Nichols MK, Powis J, Richardson D, Semret M, Stiver G, Trottier S, Valiquette L, Webster D, Ye L, McNeil SA, Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network (PCIRN) Serious Outcomes Surveillance Network and the Toronto Invasive Bacterial Diseases Network (TIBDN)

Abstract
BACKGROUND: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains.
METHODS: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100.
RESULTS: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1).
CONCLUSIONS: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

PMID: 29284435 [PubMed - indexed for MEDLINE]

Prevention and assessment of infectious diseases among children and adult migrants arriving to the European Union/European Economic Association: a protocol for a suite of systematic reviews for public health and health systems.

Mon, 05/21/2018 - 00:11
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Prevention and assessment of infectious diseases among children and adult migrants arriving to the European Union/European Economic Association: a protocol for a suite of systematic reviews for public health and health systems.

BMJ Open. 2017 Sep 11;7(9):e014608

Authors: Pottie K, Mayhew AD, Morton RL, Greenaway C, Akl EA, Rahman P, Zenner D, Pareek M, Tugwell P, Welch V, Meerpohl J, Alonso-Coello P, Hui C, Biggs BA, Requena-Méndez A, Agbata E, Noori T, Schünemann HJ

Abstract
INTRODUCTION: The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis.
METHODS AND ANALYSIS: The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
ETHICS AND DISSEMINATION: There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798.

PMID: 28893741 [PubMed - indexed for MEDLINE]

Reply: regarding business travelers.

Fri, 05/11/2018 - 00:37
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Reply: regarding business travelers.

J Travel Med. 2018 Jan 01;25(1):

Authors: Chen LH, Leder K, Schlagenhauf P, Libman M, Keystone J, Mendelson M, Gautret P, Schwartz E, Shaw M, MacDonald S, McCarthy A, Connor BA, Hamer DH, Wilson ME, GeoSentinel Surveillance Network

PMID: 29741699 [PubMed - in process]

Malaria after international travel: a GeoSentinel analysis, 2003-2016.

Thu, 05/10/2018 - 00:33
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Malaria after international travel: a GeoSentinel analysis, 2003-2016.

Malar J. 2017 Jul 20;16(1):293

Authors: Angelo KM, Libman M, Caumes E, Hamer DH, Kain KC, Leder K, Grobusch MP, Hagmann SH, Kozarsky P, Lalloo DG, Lim PL, Patimeteeporn C, Gautret P, Odolini S, Chappuis F, Esposito DH, GeoSentinel Network

Abstract
BACKGROUND: More than 30,000 malaria cases are reported annually among international travellers. Despite improvements in malaria control, malaria continues to threaten travellers due to inaccurate perception of risk and sub-optimal pre-travel preparation.
METHODS: Records with a confirmed malaria diagnosis after travel from January 2003 to July 2016 were obtained from GeoSentinel, a global surveillance network of travel and tropical medicine providers that monitors travel-related morbidity. Records were excluded if exposure country was missing or unascertainable or if there was a concomitant acute diagnosis unrelated to malaria. Records were analyzed to describe the demographic and clinical characteristics of international travellers with malaria.
RESULTS: There were 5689 travellers included; 325 were children <18 years. More than half (53%) were visiting friends and relatives (VFRs). Most (83%) were exposed in sub-Saharan Africa. The median trip duration was 32 days (interquartile range 20-75); 53% did not have a pre-travel visit. More than half (62%) were hospitalized; children were hospitalized more frequently than adults (73 and 62%, respectively). Ninety-two per cent had a single Plasmodium species diagnosis, most frequently Plasmodium falciparum (4011; 76%). Travellers with P. falciparum were most frequently VFRs (60%). More than 40% of travellers with a trip duration ≤7 days had Plasmodium vivax. There were 444 (8%) travellers with severe malaria; 31 children had severe malaria. Twelve travellers died.
CONCLUSION: Malaria remains a serious threat to international travellers. Efforts must focus on preventive strategies aimed on children and VFRs, and chemoprophylaxis access and preventive measure adherence should be emphasized.

PMID: 28728595 [PubMed - indexed for MEDLINE]

A combined experimental and computational study on the reaction of fluoroarenes with Mg-Mg, Mg-Zn, Mg-Al and Al-Zn bonds.

Fri, 05/04/2018 - 00:04
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A combined experimental and computational study on the reaction of fluoroarenes with Mg-Mg, Mg-Zn, Mg-Al and Al-Zn bonds.

Chem Sci. 2018 Feb 28;9(8):2348-2356

Authors: Bakewell C, Ward BJ, White AJP, Crimmin MR

Abstract
Through a combined experimental and computational (DFT) approach, the reaction mechanism of the addition of fluoroarenes to Mg-Mg bonds has been determined as a concerted SNAr-like pathway in which one Mg centre acts as a nucleophile and the other an electrophile. The experimentally determined Gibbs activation energy for the addition of C6F6 to a Mg-Mg bond of a molecular complex, ΔG‡298 K(experiment) = 21.3 kcal mol-1 is modelled by DFT with the ωB97X functional, ΔG‡298 K(DFT) = 25.7 kcal mol-1. The transition state for C-F activation involves a polarisation of the Mg-Mg bond and significant negative charge localisation on the fluoroarene moiety. This transition state is augmented by stabilising closed-shell Mg···F ortho interactions that, in combination with the known trends in C-F and C-M bond strengths in fluoroarenes, provide an explanation for the experimentally determined preference for C-F bond activation to occur at sites flanked by ortho-fluorine atoms. The effect of modification of both the ligand coordination sphere and the nature and polarity of the M-M bond (M = Mg, Zn, Al) on C-F activation has been investigated. A series of highly novel β-diketiminate stabilised complexes containing Zn-Mg, Zn-Zn-Zn, Zn-Al and Mg-Al bonds has been prepared, including the first crystallographic characterisation of a Mg-Al bond. Reactions of these new M-M containing complexes with perfluoroarenes were conducted and modelled by DFT. C-F bond activation is dictated by the steric accessibility, and not the polarity, of the M-M bond. The more open coordination complexes lead to enhanced Mg···F ortho interactions which in turn lower the energy of the transition states for C-F bond activation.

PMID: 29719707 [PubMed]

The ash dieback invasion of Europe was founded by two genetically divergent individuals.

Thu, 04/26/2018 - 00:11
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The ash dieback invasion of Europe was founded by two genetically divergent individuals.

Nat Ecol Evol. 2018 Apr 23;:

Authors: McMullan M, Rafiqi M, Kaithakottil G, Clavijo BJ, Bilham L, Orton E, Percival-Alwyn L, Ward BJ, Edwards A, Saunders DGO, Garcia Accinelli G, Wright J, Verweij W, Koutsovoulos G, Yoshida K, Hosoya T, Williamson L, Jennings P, Ioos R, Husson C, Hietala AM, Vivian-Smith A, Solheim H, MaClean D, Fosker C, Hall N, Brown JKM, Swarbreck D, Blaxter M, Downie JA, Clark MD

Abstract
Accelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback, is a fungal pathogen that has been moving across continents and hosts from Asian to European ash. Most European common ash trees (Fraxinus excelsior) are highly susceptible to H. fraxineus, although a minority (~5%) have partial resistance to dieback. Here, we assemble and annotate a H. fraxineus draft genome, which approaches chromosome scale. Pathogen genetic diversity across Europe and in Japan, reveals a strong bottleneck in Europe, though a signal of adaptive diversity remains in key host interaction genes. We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the ancestral polymorphism within a large source population. Subsequent introduction from this source would greatly increase adaptive potential of the pathogen. Thus, further introgression of H. fraxineus into Europe represents a potential threat and Europe-wide biological security measures are needed to manage this disease.

PMID: 29686237 [PubMed - as supplied by publisher]

Progressive multifocal leukoencephalopathy after fingolimod treatment.

Sat, 04/21/2018 - 00:14
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Progressive multifocal leukoencephalopathy after fingolimod treatment.

Neurology. 2018 Apr 18;:

Authors: Berger JR, Cree BA, Greenberg B, Hemmer B, Ward BJ, Dong VM, Merschhemke M

Abstract
OBJECTIVE: We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder.
METHODS: The Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod.
RESULTS: As of August 31, 2017, 15 fingolimod-treated patients had developed PML in the absence of natalizumab treatment in the preceding 6 months. Eleven (73%) were women and the mean age was 53 years (median: 53 years). Fourteen of the 15 patients were treated with fingolimod for >2 years. Two patients had confounding medical conditions. Two patients had natalizumab treatment. This included one patient whose last dose of natalizumab was 3 years and 9 months before the diagnosis of PML. The second patient was receiving fingolimod for 4 years and 6 months, which was discontinued to start natalizumab and was diagnosed with PML 3 months after starting natalizumab. Absolute lymphocyte counts were available for 14 of the 15 patients and none exhibited a sustained grade 4 lymphopenia (≤200 cells/μL).
CONCLUSIONS: The risk of PML with fingolimod in the absence of prior natalizumab treatment is low. The estimated risk was 0.069 per 1,000 patients (95% confidence interval: 0.039-0.114), and the estimated incidence rate was 3.12 per 100,000 patient-years (95% confidence interval: 1.75-5.15). Neither clinical manifestations nor radiographic features suggested any unique features of fingolimod-associated PML.

PMID: 29669908 [PubMed - as supplied by publisher]

Plant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages.

Thu, 04/19/2018 - 01:01
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Plant-made virus-like particles bearing influenza hemagglutinin (HA) recapitulate early interactions of native influenza virions with human monocytes/macrophages.

Vaccine. 2017 08 16;35(35 Pt B):4629-4636

Authors: Makarkov AI, Chierzi S, Pillet S, Murai KK, Landry N, Ward BJ

Abstract
INTRODUCTION: Plant-made virus-like particles (VLP) bearing influenza virus hemagglutinins (HA) are novel vaccine candidates that induce cross-reactive humoral and poly-functional T cell responses. To better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of VLPs bearing either H1 (A/California/07/2009 (H1N1)) or H5 (A/Indonesia/05/2005 (H5N1)) with a human monocytoid cell line (U-937 cells) and human monocyte-derived macrophages (MDMs) as model antigen-presenting cells (APC).
METHODS AND RESULTS: Using Vibrio cholerae sialidase and lectins that target α2,6- (Sambucus nigra lectin) or α2,3-linked sialic acids (Maackia amurensis lectin I), we demonstrated that VLPs bind to these APCs in a sialic acid-dependent manner. Using lysosomal markers and DiD-labelled VLPs, we found that attachment to the cell surface leads to internalization, trafficking to acidic cell compartments and fusion of the VLP lipid envelope with endosomal membranes. Incubation of MDMs with H1- but not H5-VLPs induced proliferation of autologous peripheral blood mononuclear cells suggesting antigen processing and stimulation of a memory T cell response.
CONCLUSIONS: Plant-made VLPs bearing influenza HA not only mimic the structure of influenza virions to some degree but also recapitulate key features of the initial virus-APC interaction. These observations may help to explain the balanced humoral and cellular responses to plant-made VLP vaccines.

PMID: 28712489 [PubMed - indexed for MEDLINE]

Point-of-care and point-of-"can": Leveraging reference-laboratory capacity for integrated diagnosis of fever syndromes in the tropics.

Sun, 04/15/2018 - 00:56
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Point-of-care and point-of-"can": Leveraging reference-laboratory capacity for integrated diagnosis of fever syndromes in the tropics.

Clin Microbiol Infect. 2018 Apr 09;:

Authors: Semret M, Ndao M, Jacobs J, Yansouni CP

Abstract
BACKGROUND: There is an urgent need for integrated diagnosis of febrile syndromes, able to account for multiple pathogens and inform decisions for clinical care and public health.
AIMS: To reflect on the evolving roles of laboratory-based testing for non-malarial febrile illnesses (NMFI) in low-resource settings (LRS), and to consider how advances in diagnostics, in connectivity and transport, and in quality-systems implementation may substantially enhance the capacity of reference laboratories to bridge the current gap between remote passive surveillance and clinically meaningful integrated fever diagnosis.
SOURCES: Iterative search of PubMed databases, organisational reports, and expert consultation.
CONTENT: Implementation of new technologies such as very broad molecular panels for surveillance and mass spectrometry may considerably diminish capability gaps in LRS reference laboratories. Although the need for clinical bacteriology diagnostics is now recognized, lack of new simple and rapid phenotypic tests for antimicrobial resistance remains a key deficiency. Several initiatives to strengthen diagnostic preparedness for infectious disease outbreaks have highlighted the need for functional tiered laboratory networks. Recently, dramatic headway in connectivity, such as combining automated readers with the image processing and data transmission capabilities of smartphones, now allows for more complex testing and interfacing with distant laboratory information systems, while reducing workload and errors. Together with connectivity to transmit and receive results, new approaches to specimen collection and transport - such as the validation of rectal swabs and the use of aerial drones to transport specimens to distant laboratories - now make remote testing feasible. The above innovations also open the possibility of implementing quality systems through community-level diagnostic stewardship. Finally, strengthened laboratory networks actively support the feasibility of implementing quality-assured point-of-care testing where it is needed.
IMPLICATIONS: Recent advances offer the present-day possibility of innovations to re-invent the relationship between distant reference laboratories and end-users for integrated diagnosis of NMFI.

PMID: 29649602 [PubMed - as supplied by publisher]

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

Fri, 04/13/2018 - 01:11
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The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

Euro Surveill. 2018 Apr;23(14):

Authors: Greenaway C, Pareek M, Abou Chakra CN, Walji M, Makarenko I, Alabdulkarim B, Hogan C, McConnell T, Scarfo B, Christensen R, Tran A, Rowbotham N, van der Werf MJ, Noori T, Pottie K, Matteelli A, Zenner D, Morton RL

Abstract
BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

PMID: 29637889 [PubMed - in process]

The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review.

Fri, 04/13/2018 - 01:11
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The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review.

Euro Surveill. 2018 Apr;23(14):

Authors: Greenaway C, Pareek M, Abou Chakra CN, Walji M, Makarenko I, Alabdulkarim B, Hogan C, McConnell T, Scarfo B, Christensen R, Tran A, Rowbotham N, Noori T, van der Werf MJ, Pottie K, Matteelli A, Zenner D, Morton RL

Abstract
BACKGROUND: The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source country (19-336) and screening setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion: Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.

PMID: 29637888 [PubMed - in process]

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