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Journal articleLazarus RP, John J, Shanmugasundaram E, et al., 2017,
The effect of probiotics and zinc supplementation on the immune response to oral rotavirus vaccine: A randomized, factorial design, placebo-controlled study among Indian infants
, Vaccine, Vol: 36, Pages: 273-279, ISSN: 0264-410XBackgroundStrategies are needed to improve oral rotavirus vaccine (RV), which provides suboptimal protection in developing countries. Probiotics and zinc supplementation could improve RV immunogenicity by altering the intestinal microbiota and immune function.MethodsInfants 5 weeks old living in urban Vellore, India were enrolled in a randomized, double-blind, placebo-controlled trial with a 4-arm factorial design to assess the effects of daily zinc (5 mg), probiotic (1010 Lactobacillus rhamnosus GG) or placebo on the immunogenicity of two doses of RV (Rotarix®, GlaxoSmithKline Biologicals) given at 6 and 10 weeks of age. Infants were eligible for participation if healthy, available for the study duration and without prior receipt of RV or oral poliovirus vaccine other than the birth dose. The primary outcome was seroconversion to rotavirus at 14 weeks of age based on detection of VP6-specific IgA at ≥20 U/ml in previously seronegative infants or a fourfold rise in concentration.ResultsThe study took place during July 2012 to February 2013. 620 infants were randomized equally between study arms and 551 (88.9%) completed per protocol. Seroconversion was recorded in 54/137 (39.4%), 42/136 (30.9%), 40/143 (28.0%), and 37/135 (27.4%) infants receiving (1) probiotic and zinc, (2) probiotic and placebo, (3) placebo and zinc, (4) two placebos. Seroconversion showed a modest improvement among infants receiving probiotic (difference between groups 1, 2 and 3, 4 was 7.5% (97.5% Confidence Interval (CI): −1.4%, 16.2%), p = 0.066) but not zinc (difference between groups 1, 3 and 2, 4 was 4.4% (97.5% CI: −4.4%, 13.2%), p = 0.272). 16 serious adverse events were recorded, none related to study interventions.ConclusionsZinc or probiotic supplementation did not significantly improve the low immunogenicity of rotavirus vaccine given to infants in a poor urban community in India. A modest effect of combined supplementation deserves further investigation.
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Conference paperChow NA, Gade L, Lockhart S, et al., 2017,
Using whole-genome sequencing to elucidate the epidemiology of the globally emerging, multidrug-resistant yeast Candida auris
, 8th Trends in Medical Mycology, Publisher: WILEY, Pages: 21-21, ISSN: 0933-7407 -
Journal articleZhang X-S, Pebody R, Charlett A, et al., 2017,
Estimating and modelling the transmissibility of Middle East Respiratory Syndrome CoronaVirus during the 2015 outbreak in the Republic of Korea
, INFLUENZA AND OTHER RESPIRATORY VIRUSES, Vol: 11, Pages: 434-444, ISSN: 1750-2640- Author Web Link
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- Citations: 18
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Journal articleSmallbone WA, Chadwick EA, Francis J, et al., 2017,
East-West Divide: temperature and land cover drive spatial variation of <i>Toxoplasma gondii</i> infection in Eurasian otters (<i>Lutra lutra</i>) from England and Wales
, PARASITOLOGY, Vol: 144, Pages: 1433-1440, ISSN: 0031-1820- Cite
- Citations: 8
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Journal articleHickman R, Van Verk MC, Van Dijken AJH, et al., 2017,
Architecture and Dynamics of the Jasmonic Acid Gene Regulatory Network
, PLANT CELL, Vol: 29, Pages: 2086-2105, ISSN: 1040-4651- Author Web Link
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- Citations: 163
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Journal articleBhatt S, Cameron E, Flaxman SR, et al., 2017,
Improved prediction accuracy for disease risk mapping using Gaussian process stacked generalization.
, Interface, Vol: 14, ISSN: 1742-5662Maps of infectious disease-charting spatial variations in the force of infection, degree of endemicity and the burden on human health-provide an essential evidence base to support planning towards global health targets. Contemporary disease mapping efforts have embraced statistical modelling approaches to properly acknowledge uncertainties in both the available measurements and their spatial interpolation. The most common such approach is Gaussian process regression, a mathematical framework composed of two components: a mean function harnessing the predictive power of multiple independent variables, and a covariance function yielding spatio-temporal shrinkage against residual variation from the mean. Though many techniques have been developed to improve the flexibility and fitting of the covariance function, models for the mean function have typically been restricted to simple linear terms. For infectious diseases, known to be driven by complex interactions between environmental and socio-economic factors, improved modelling of the mean function can greatly boost predictive power. Here, we present an ensemble approach based on stacked generalization that allows for multiple nonlinear algorithmic mean functions to be jointly embedded within the Gaussian process framework. We apply this method to mapping Plasmodium falciparum prevalence data in sub-Saharan Africa and show that the generalized ensemble approach markedly outperforms any individual method.
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Journal articleVolz EM, Frost SDW, 2017,
Scalable relaxed clock phylogenetic dating
, Virus Evolution, Vol: 3, ISSN: 2057-1577Molecular clock models relate observed genetic diversity to calendar time, enabling estimation of times of common ancestry. Many large datasets of fast-evolving viruses are not well fitted by molecular clock models that assume a constant substitution rate through time, and more flexible relaxed clock models are required for robust inference of rates and dates. Estimation of relaxed molecular clocks using Bayesian Markov chain Monte Carlo is computationally expensive and may not scale well to large datasets. We build on recent advances in maximum likelihood and least-squares phylogenetic and molecular clock dating methods to develop a fast relaxed-clock method based on a Gamma-Poisson mixture model of substitution rates. This method estimates a distinct substitution rate for every lineage in the phylogeny while being scalable to large phylogenies. Unknown lineage sample dates can be estimated as well as unknown root position. We estimate confidence intervals for rates, dates, and tip dates using parametric and non-parametric bootstrap approaches. This method is implemented as an open-source R package, treedater.
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Journal articleWatson O, Slater HC, Verity R, et al., 2017,
Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa
, eLife, Vol: 6, ISSN: 2050-084XRapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of pfhrp2-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed pfhrp2-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% pfhrp2-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of pfhrp2-deletion, and identify the geographic regions in which surveillance for pfhrp2-deletion should be prioritised.
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Conference paperKatzelnick LC, Harris E, 2017,
Immune correlates of protection for dengue: State of the art and research agenda
, Publisher: ELSEVIER SCI LTD, Pages: 4659-4669, ISSN: 0264-410X- Author Web Link
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- Citations: 78
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Journal articleParker EPK, Praharaj I, John J, et al., 2017,
Changes in the intestinal microbiota following the administration of azithromycin in a randomised placebo-controlled trial among infants in south India
, Scientific Reports, Vol: 7, ISSN: 2045-2322Macrolides are among the most widely prescribed antibiotics worldwide. However, their impact on the gut’s bacterial microbiota remains uncertain. We characterised the intestinal microbiota in 6–11 month-old infants in India who received a 3-day course of azithromycin or placebo during a randomised trial of oral poliovirus vaccine immunogenicity (CTRI/2014/05/004588). In 60 infants per study arm, we sequenced the V4 region of the bacterial 16S rRNA gene in stool samples collected before and 12 days after finishing treatment. We also tested for the presence of common bacterial, viral, and eukaryotic enteropathogens in the same samples using real-time PCR in a Taqman array card (TAC) format. Azithromycin induced a modest decline in microbiota richness and a shift in taxonomic composition driven by a reduction in the relative abundance of Proteobacteria and Verrucomicrobia (specifically Akkermansia muciniphila). The former phylum includes pathogenic strains of Escherichia coli and Campylobacter spp. that declined in prevalence based on the TAC assay. These findings differ from previous observations among older children and adults in Europe and North America, suggesting that the effects of azithromycin on the bacterial flora may be specific to the age and geographic setting of its recipients.
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