Informal genomic surveillance of regional distribution of Salmonella Typhi genotypes and antimicrobial resistance via returning travellers
Contributors: Ingle, Danielle J., Nair, Satheesh, Hartman, Hassan, Ashton, Philip M., Dyson, Zoe A., Day, Martin, Freedman, Joanne, Chattaway, Marie A., Holt, Kathryn E., Dallman, Timothy J.
... Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever, a systemic human infection with a burden exceeding 20 million cases each year that occurs disproportionately among children in low and middle income countries. Antimicrobial therapy is the mainstay for treatment, but resistance to multiple agents is common. Here we report genotypes and antimicrobial resistance (AMR) determinants detected from routine whole-genome sequencing (WGS) of 533 S. Typhi isolates referred to Public Health England between April 2014 and March 2017, 488 (92%) of which had accompanying patient travel information obtained via an enhanced surveillance questionnaire. The majority of cases involved S. Typhi 4.3.1 (H58) linked with travel to South Asia (59%). Travel to East and West Africa were associated with genotypes 4.3.1 and 3.3.1, respectively. Point mutations in the quinolone resistance determining region (QRDR), associated with reduced susceptibility to fluoroquinolones, were very common (85% of all cases) but the frequency varied significantly by region of travel: 95% in South Asia, 43% in East Africa, 27% in West Africa. QRDR triple mutants, resistant to ciprofloxacin, were restricted to 4.3.1 lineage II and associated with travel to India, accounting for 23% of cases reporting travel to the country. Overall 24% of isolates were MDR, however the frequency varied significantly by region and country of travel: 27% in West Africa, 52% in East Africa, 55% in Pakistan, 24% in Bangladesh, 3% in India. MDR determinants were plasmid-borne (IncHI1 PST2 plasmids) in S. Typhi 3.1.1 linked to West Africa, but in all other regions MDR was chromosomally integrated in 4.3.1 lineage I. We propose that routine WGS data from travel-associated cases in industrialised countries could serve as informal sentinel AMR genomic surveillance data for countries where WGS is not available or routinely performed.
Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis
Contributors: Aibana, Omowunmi, Huang, Chuan-Chin, Aboud, Said, Arnedo-Pena, Alberto, Becerra, Mercedes C, Bellido-Blasco, Juan Bautista, Bhosale, Ramesh, Calderon, Roger, Chiang, Silvia, Contreras, Carmen
... Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.
Data and code from: Estimating the burden of dengue and the impact of release of wMel Wolbachia infected mosquitoes in Indonesia: a modelling study
Contributors: O'reilly, Kathleen, Hendrickx, Emilie, Kharisma, Dinar D., Wilastonegoro, Nandyan N., Carrington, Lauren B., Elyazar, Iqbal R. F., Kucharsk, Adam J., Lowe, Rachel, Flasche, Stefan, Pigott, David M.
... Wolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact of Wolbachia are critical in guiding funder and government decisions on its future wider use.
Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex
Contributors: Chiner-Oms, Álvaro, Berney, Michael, Boinett, Christine, González-Candelas, Fernando, Young, Douglas B, Gagneux, Sebastien, Jacobs Jr, William R., Parkhill, Julian, Cortes, Teresa, Comas, Iñaki
... The Mycobacterium tuberculosis complex (MTBC) members display different host-specificities and virulence phenotypes. Here, we have performed a comprehensive RNAseq and methylome analysis of the main clades of the MTBC and discovered unique transcriptional profiles. The majority of genes differentially expressed between the clades encode proteins involved in host interaction and metabolic functions. A significant fraction of changes in gene expression can be explained by positive selection on single mutations that either create or disrupt transcriptional start sites (TSS). Furthermore, we show that clinical strains have different methyltransferases inactivated and thus different methylation patterns. Under the tested conditions, differential methylation has a minor direct role on transcriptomic differences between strains. However, disruption of a methyltransferase in one clinical strain revealed important expression differences suggesting indirect mechanisms of expression regulation. Our study demonstrates that variation in transcriptional profiles are mainly due to TSS mutations and have likely evolved due to differences in host characteristics.
Contributors: Arunga, Simon
... This dataset contains descriptive data of health facilities in South western Uganda, locations, staffing levels, equipment, consumables and drug stocks as well as the knowledge of the health workers in those facilities in managing microbial keratitis.
Contributors: Schwabl, Philipp, Imamura, Hideo, Van den Broeck, Frederik, Costales, Jaime A, Maiguashca-Sánchez, Jalil, Miles, Michael, Andersson, Bjorn, Grijalva, Mario J, Llewellyn, Martin S
... Genetic exchange enables parasites to rapidly transform disease phenotypes and exploit new host populations. Trypanosoma cruzi, the parasitic agent of Chagas disease and a public health concern throughout Latin America, has for decades been presumed to exchange genetic material rarely and without classic meiotic sex. We present compelling evidence from 45 genomes sequenced from southern Ecuador that T. cruzi in fact maintains truly sexual, panmictic groups that can occur alongside others that remain highly clonal after past hybridization events. These groups with divergent reproductive strategies appear genetically isolated despite possible co-occurrence in vectors and hosts. We propose biological explanations for the fine-scale disconnectivity we observe and discuss the epidemiological consequences of flexible reproductive modes. Our study reinvigorates the hunt for the site of genetic exchange in the T. cruzi life cycle, provides tools to define the genetic determinants of parasite virulence, and reforms longstanding theory on clonality in trypanosomatid parasites.
Contributors: Cooper, Laura, Yun Kang, Su, Bisanzio, Donal, Maxwell, Kilama, Rodriguez-Barraquer, Isabel, Greenhouse, Bryan, Drakeley, Chris, Arinaitwe, Emmanuel, Staedke, Sarah, Gething, Peter W
... Uganda_data.csv: The dataset contains mosquito count data from monthly entomological surveillance conducted at 330 households between 2011 and 2016 for three study sites in Uganda. Uganda_housing_covariates.dta: The data file contains household-level housing covariates for the three study sites in Uganda, including roof type, wall type, floor type, open/closed eaves, types of airbricks, and house type. Site IDs and household IDs are also available. TororoHH_info.xlsx: A full list of enumerated households in Tororo, Uganda. KanunguHH_info.xlsx: A full list of enumerated households in Kanungu, Uganda. JinjaHH_info.xlsx: A full list of enumerated households in Jinja, Uganda. Uganda_environmental_covariates.csv: Environmental covariate data for three study sites in Uganda.
Semi-field evaluation of the cumulative effects of a “Lethal House Lure” on malaria mosquito mortality
Contributors: Barreaux, Antoine M. G., Oumbouke, Welbeck, Zran Tia, Innocent, Brou, N’guessan, Koffi, Alphonsine A., N'guessan, Raphael, Thomas, Matthew B
... There is growing interest in the potential to modify houses to target mosquitoes with insecticides or repellents as they search for human hosts. One version of this ‘Lethal House Lure’ approach is the In2Care® EaveTube, which consists of a section of polyvinyl chloride (PVC) pipe fitted into a closed eave, with an insert comprising electrostatic netting treated with insecticide powder placed inside the tube. Preliminary evidence suggests that when combined with screening of doors and windows, there is a reduction in entry of mosquitoes and an increase in mortality. However, the rate of overnight mortality remains unclear. The current study used a field enclosure built around experimental huts to investigate the mortality of cohorts of mosquitoes over multiple nights.
Replication Data for: Impact of the introduction of rotavirus vaccine on hospital admissions for diarrhoea among children in Kenya: A controlled interrupted time series analysis
Contributors: Otieno, Grieven P., Bottomley, Christian, Khagayi, Sammy, Ogwel, Billy, Nokes, D. James
... These data include monthly counts of hospital admissions in Kilifi county hospital and Siaya county and referral hospital among children aged <5 years and residents of either the Kilifi Health and Demographic surveillance system or the Siaya Health and Demographic surveillance system. The admissions monthly counts are stratified into all admissions, all cause diarrhea and rotavirus cases. In addition, mid-year population estimates, categorical variables for months affected by health workers industrial actions and infections used to generate synthetic controls(rotavirus negatives, malaria and pneumonia) are included. The dataset was used to evaluate the impact of rotavirus vaccine among children aged <5 years in the two HDSS.
Conjunctival Microbiome-Host Responses Are Associated With Impaired Epithelial Cell Health in Both Early and Late Stages of Trachoma
Contributors: Pickering, Harry, Palmer, Christine D, Houghton, Joanna, Makalo, Pateh, Joof, Hassan, Derrick, Tamsyn, Goncalves, Adriana, Mabey, David, Bailey, Robin, Burton, Matthew
... Trachoma, a neglected tropical disease, is the leading infectious cause of blindness and visual impairment worldwide. Host responses to ocular chlamydial infection resulting in chronic inflammation and expansion of non-chlamydial bacteria are hypothesized risk factors for development of active trachoma and conjunctival scarring