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
A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia
Contributors: James, Philip, Jawla, Ousubie, Mohammed, Nuredin, Ceesay, Kabiru, Akemokwe, Fatai, Sonko, Bakary, Sise, Ebrima, Prentice, Andrew, Silver, Matt
... Infant DNA methylation profiles are associated with their mother’s periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials.
CYP2D6 polymorphisms and the safety and gametocytocidal activity of single dose primaquine for P. falciparum
Contributors: Pett, Helmi, Bradley, John, Okebe, Joseph, Dicko, Alassane, Tiono, Alfred B, Goncalves, Bronner, Stone, Will J. R., Chen, Ingrid, Lanke, Kjerstin, Neuvonen, Mikko
... Single dose primaquine (PQ) clears mature gametocytes and reduces transmission of Plasmodium falciparum after artemisinin combination therapy. Genetic variation in CYP2D6, the gene producing the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6), influences plasma concentrations of PQ and its metabolites and is associated with PQ treatment failure in P. vivax. Using blood and saliva samples of varying quantity and quality from 8 clinical trials across Africa, (n=1076), we were able to genotype CYP2D6 for 774 samples (72%). We determined whether genetic variation in CYP2D6 has implications for PQ efficacy in individuals with gametocytes at the time of PQ administration (n=554) and for safety in Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals treated with PQ (n=110). Individuals with genetically inferred CYP2D6 poor/intermediate metabolizer status had higher gametocyte prevalence on day 7 or 10 post PQ compared to those with extensive/ultrarapid CYP2D6 metabolizer status (OR = 1.79 [1.10, 2.90], p = 0.018). Mean minimum haemoglobin concentration during follow-up for G6PD deficient individuals was 11.8 g/dL for CYP2D6 extensive/ultrarapid metabolizers and 12.1 g/dL for CYP2D6 poor/intermediate metabolizers (p = 0. 803). CYP2D6 genetically inferred metabolizer status was also not associated with anaemia following PQ treatment. (p = 0.331). We conclude that CYP2D6 poor/intermediate metabolizer status may be associated with prolonged gametocyte carriage after treatment with single low dose PQ but not with treatment safety.