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bioRxiv2020

Dynamics of mcr-1 prevalence and mcr-1-positive Escherichia coli after the cessation of colistin use as a feed additive for animals in China: a prospective cross-sectional and whole genome sequencing based molecular epidemiological study

BackgroundThe global dissemination of colistin resistance encoded by mcr-1 has been attributed to extensive use of colistin in livestock, threatening colistin efficacy in medicine. The emergence of mcr-1 in common pathogens, such as Escherichia coli, is of particular concern. Therefore, China banned the use of colistin in animal feed from May 1ST 2017. We investigated subsequent changes in mcr-1 prevalence, and the genomic epidemiology of mcr-1-positive Escherichia coli (MCRPEC). MethodsSampling was conducted pre- (October-December 2016) and post-colistin ban (October-December, 2017 and 2018, respectively). 3675 non-duplicate pig fecal samples were collected from 14 provinces (66 farms) in China to determine intervention-related changes in mcr-1 prevalence. 15193 samples were collected from pigs, healthy human volunteers, colonized and infected hospital inpatients, food and the environment in Guangzhou, to characterize source-specific mcr-1 prevalence and the wider ecological impact of the ban. From these samples, 688 MCRPEC were analyzed with whole genome sequencing (WGS), plasmid conjugation and S1-PFGE/Southern blots to characterize associated genomic changes. FindingsAfter the ban, mcr-1 prevalence decreased significantly in national pig farms, from 45{middle dot}0% (308/684 samples) in 2016, to 19{middle dot}4% (274/1416) in 2018 (p<0{middle dot}0001). This trend was mirrored in samples from most sources in Guangzhou (overall 19{middle dot}2% [959/5003 samples] in 2016; 5{middle dot}3% [238/4489] in 2018; p<0{middle dot}0001). The population structure of MCRPEC was diverse (23 sequence clusters [SCs]); ST10 clonal complex isolates were predominant (247/688 [36%]). MCRPEC causing infection in hospitalized inpatients were genetically more distinct and appeared less affected by the ban. mcr-1 was predominantly found on plasmids (632/688 [92%]). Common mcr-1 plasmid types included IncX4, IncI2 and IncHI2 (502/656 [76.5%]); significant increases in IncI2-associated mcr-1 and a distinct lineage of mcr-1-associated IncHI2 were observed post-ban. Changes in the frequency of mcr-1-associated flanking sequences (ISApl1-negative MCRPEC), 63 core genome SNPs and 30 accessory genes were also significantly different after the ban, consistent with rapid genetic adaptation in response to changing selection pressures. InterpretationA rapid, ecosystem-wide, decline in mcr-1 was observed after banning the use of colistin in animal feed, with associated genetic changes in MCRPEC. Genomic surveillance is key to assessing and monitoring stewardship interventions. FundingNational Natural Science Foundation of China

microbiology↗

bioRxiv2020

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

BackgroundGenome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To better understand etiological pathways that might lead to discovery of new treatments or prevention strategies, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome while also exploring associations with common variants. Methods and ResultsUsing samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants and myocardial infarction (MI), coronary heart disease (CHD), and all-cause mortality following these events. Single variant and gene-based analyses were performed separately in each cohort and then meta-analyzed for each outcome. A low-frequency intronic variant (rs988583) in PLCL1 was significantly associated with prevalent MI (OR=1.80, 95% confidence interval: 1.43, 2.27; P=7.12 x 10-7). Three common variants, rs9349379 in PHACTR1, and rs1333048 and rs4977574 in the 9p21 region, were significantly associated with prevalent CHD. Four common variants (rs4977574, rs10757278, rs1333049, and rs1333048) within the 9p21 locus were significantly associated with incident MI. We conducted gene-based burden tests for genes with a cumulative minor allele count (cMAC) [≥] 5 and variants with minor allele frequency (MAF) < 5%. TMPRSS5 and LDLRAD1 were significantly associated with prevalent MI and CHD, respectively, and RC3H2 and ANGPTL4 were significantly associated with incident MI and CHD, respectively. No loci were significantly associated with all-cause mortality following a MI or CHD event. ConclusionThis study confirmed previously reported loci influencing heart disease risk, and one single variant and three genes associated with MI and CHD were newly identified and warrant future investigation.

genetics↗

bioRxiv2020

Clinical and genomic epidemiology of carbapenem-non-susceptible Citrobacter spp. at a tertiary healthcare center over two decades

Carbapenem-non-susceptible Citrobacter spp. (CNSC) are increasingly recognized as healthcare-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000-2018 for CNSC, as defined by ertapenem non-susceptibility. Over this timeframe, the proportion of CNSC increased from 4% to 10% (P=0.03), as did carbapenem daily defined doses/1000 patient days (6.52 to 34.5, R2=0.831, P<0.001), which correlated with the observed increase in CNSC (lag=0 years, R2=0.660). Twenty CNSC isolates from 19 patients at PUH and other UPMC hospitals were available for further analysis, including whole-genome short-read sequencing and additional antimicrobial susceptibility testing. Of the 19 patients, nearly all acquired CNSC in the healthcare setting and over half had polymicrobial cultures containing at least one other organism. Among the 20 CNSC isolates, C. freundii was the predominant species identified (60%). CNSC genomes were compared with genomes of carbapenem-susceptible Citrobacter spp. from UPMC, and with other publicly available CNSC genomes. Isolates encoding carbapenemases (blaKPC-2, blaKPC-3, and blaNDM-1) were also long-read sequenced, and their carbapenemase-encoding plasmid sequences were compared with one another and with publicly available sequences. Phylogenetic analysis of 102 UPMC Citrobacter spp. genomes showed that CNSC from our setting did not cluster together. Similarly, a global phylogeny of 64 CNSC genomes showed a diverse population structure. Our findings suggest that both local and global CNSC populations are genetically diverse, and that CNSC harbor carbapenemase-encoding plasmids found in other Enterobacterales.

microbiology↗

bioRxiv2020

Prospects for detecting early warning signals in discrete event sequence data: application to epidemiological incidence data.

Early warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators. Author summaryThe threat posed by infectious diseases has a huge impact on our global society. It is therefore critical to monitor infectious diseases as new data become available during control campaigns. One obstacle in observing disease emergence or elimination is understanding what influences noise in the data and how this fluctuates when near to zero cases. The standard data type collected is the number of new cases per day/month/year but mathematical modellers often focus on data such as the total number of infectious people, due to its analytical properties. We have developed a methodology to monitor the standard type of data to inform whether a disease is approaching emergence or disease elimination. We have shown computationally how fluctuations change as disease data get closer towards a tipping point and our insights highlight how these observed changes can be strikingly different when calculated on different types of data.

ecology↗

bioRxiv2020

Nairobi Sheep Disease Virus: a historical and epidemiological perspective

Nairobi Sheep Disease virus (NSDv) is a zoonotic and tick-borne disease that can cause over 90% mortality in small ruminants. NSDv has historically circulated in East Africa and has recently emerged in the Asian continent. Despite efforts to control the disease, some regions, mostly in warmer climates, persistently report disease outbreaks. Consequently, it is necessary to understand how environmental tolerances and factors that influence transmission may shed light on its possible emergence in other regions. In this study, we quantified the available literature of NSDv from which occurrence data was extracted. In total, 308 locations from Uganda, Kenya, Tanzania, Somalia, India, Sri Lanka and China were coupled with landscape conditions to reconstruct the ecological conditions for NSDv circulation and identify areas of potential disease transmission risk. Our results identified areas suitable for NSDv in Ethiopia, Malawi, Zimbabwe, Southeastern China, Taiwan, and Vietnam. Unsuitable areas included Democratic Republic of Congo, Zambia, and Southern Somalia. In summary, soil moisture, livestock density, and precipitation predispose certain areas to NSDv circulation. It is critical to investigate the epidemiology of NSDv in order to promote better allocation of resources to control its spread in regions that are more at risk. This will help reduce disease impact worldwide as climate change will favor emergence of such vector-borne diseases in areas with dense small ruminant populations.

ecology↗

bioRxiv2020

Genomic Epidemiology of Escherichia coli Isolates from a Tertiary Referral Center in Lilongwe, Malawi

Antimicrobial resistance (AMR) is a global threat, including in sub-Saharan Africa. However, little is known about the genetics of resistant bacteria in the region. In Malawi, there is growing concern about increasing rates of antimicrobial resistance to most empirically used antimicrobials. The highly drug resistant Escherichia coli sequence type (ST) 131, which is associated with the extended spectrum {beta}-lactamase blaCTX-M-15, has been increasing in prevalence globally. Previous data from isolates collected between 2006-2013 in southern Malawi have shown the presence of ST131 and the blaCTX-M-15 gene in the country. We performed whole genome sequencing (WGS) of 58 clinical E. coli isolates at Kamuzu Central Hospital, a tertiary care center in central Malawi, collected from 2012-2018. We used Oxford Nanopore Technologies (ONT) sequencing, which was performed in Malawi. We show that ST131 has become more prevalent (14.9% increasing to 32.8%) and that the blaCTX-M-15gene is occurring at a higher frequency (21.3% increasing to 44.8%). Phylogenetics show isolates are highly related between the central and southern geographic regions and confirm that ST131 isolates are contained in a single group consistent with recent expansion. All AMR genes, including blaCTX-M-15, were widely distributed across sequence types. We also identified an increased number of ST410 isolates, which in this study tend to carry a plasmid-located copy of blaCTX-M-15 gene at a higher frequency than blaCTX-M-15 occurs in ST131. This study confirms the expanding nature of ST131 and the wide distribution of the blaCTX-M-15 gene in Malawi. We also highlight the feasibility of conducting longitudinal genomic epidemiology studies of important bacteria with the sequencing done on site using a nanopore platform that requires minimal infrastructure. DATA SUMMARYThe sequencing data used for this analysis is available in public data repositories. Information on the sequences used is provided in Supplementary Table 2.

genetics↗

bioRxiv2020

Epidemiological study on foot-and-mouth disease in small ruminants: sero-prevalence and risk factor assessment in Kenya

Foot-and-mouth disease (FMD) is endemic in Kenya affecting cloven-hoofed ruminants. The epidemiology of the disease in small ruminants (SR) is not documented. We carried out a cross-sectional study, the first in Kenya, to estimate the sero-prevalence of FMD in SR and the associated risk factors nationally. Selection of animals to be sampled used a multistage cluster sampling approach. Serum samples totaling 7564 were screened for FMD antibodies of Non-Structural-Proteins using ID Screen(R) NSP Competition ELISA kit. Data were analysed using Statistical Package for Social Studies Version 20. To identify the risk factors, chi-square and logistic regression analyses were used. The country animal level sero-prevalence was 23.3% (95% CI: 22.3-24.3%) while herd level sero-prevalence was 77.6% (95% CI: 73.9-80.9%). Sero-positivity was significantly higher in the pastoral zone (31.5%) than in the sedentary zone at 14.5% ({chi}2 =303.2, p<0.05). In the most parsimonious backward fitting logistic multivariable regression, the only risk factors that were significantly positively associated with FMD sero-positivity in SR were multipurpose (OR=1.150; p=0.034) and dairy production types (OR=2.029; p=0.003). Those that were significantly negatively associated with FMD sero-positivity were male sex (OR=0.856; p=0.026), young age (OR=0.601; p=0.037), sedentary production zone (OR=0.471; p<0.001), bringing in of SR (OR=0.838; p=0.004), purchase of SR from market/middlemen (OR=0.877; p=0.049), no interaction with wildlife (OR=0.657; p<0.001), mixed production type (OR=0.701; p=0.016), enclosure of SR day and night (OR=0.515; p=0.001), migratory grazing system (OR=0.807; p=0.047), on-farm watering system (OR=0.724; p=0.002), male-from-another-farm (OR=0.723; p=0.030) and artificial insemination (OR=0.357; p=0.008) breeding methods. This study showed that there is widespread undetected virus circulation in SR indicated by ubiquitous spatial distribution of significant FMD sero-positivity in the country. The risk factors were mainly husbandry related. Strengthening of risk-based FMD surveillance in carrier SR which pose potential risk of virus transmission to other susceptible species is recommended. Adjustment of husbandry practices to control FMD in SR and in-contact species is suggested. Cross-transmission and more risk factors need to be researched.

microbiology↗

bioRxiv2020

Molecular epidemiology and clone transmission of carbapenem-resistant Acinetobacter baumannii in ICU rooms

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates on intensive care unit surfaces from one hospital in China collected over six years. All strains carried blaOXA-23, blaOXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor and insertion sequences burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates was dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only present in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in hospital ICU environment, demonstrated potential clone outbreak in hospital.

bioinformatics↗

bioRxiv2020

Baseline epidemiology and associated dog ecology study towards stepwise elimination of rabies in Kwara state, Nigeria

Understanding domestic dog population dynamics and ecology is necessary for any effective rabies control program. This study was conducted as part of the baseline epidemiological studies necessary for the establishment of the Kwara Rabies Rapid Alert System "KRRAS". The aim of this study was to determine the dog population structure of Kwara State by assessing the dog ownership, vaccination status, and prevalence of dog bites. A total of 1,460 questionnaires were administered to respondents in the three senatorial zones of the state using Open Data Kit (ODK) between June 2019 to January 2020. Of the 1460 households surveyed, 293 (20.1%) owned at least one dog with an average of 2.25 dogs per household. The male to female ratio was 2.2:1 and 85% (n=250/293) of the owned dogs were local breeds. A total of 785 dogs was enumerated (659 dogs from 293 households and 126 free-roaming dogs) and 7811 persons which resulted in a dog-human ratio of 1:9.95. The estimated dog population is 376,789 (95% CI: 343,700 - 379,878). The dog anti-rabies vaccination coverage was 31% (n=92/293). The prevalence of dog-bite was 13% (n=193/1460) of which only 27% of the victims (n=61/225) received post-exposure prophylaxis (PEP). The ethnicity of respondents had a significant impact on dog ownership. Yorubas more often (OR: 2.2-5; 95% CI: 1.2 - 12.4; p < 0.001) owned dogs than other tribes. The vaccination status of owned dogs was greatly impacted by the level of education of the respondents (OR: 5.03; 95% CI: 1.5073 - 16.8324; p < 0.001); the breed of the dog with exotic dogs being more vaccinated (OR: 2.8; 95% CI: 0.7150 - 10.857; p < 0.001) and the confinement of the dog (OR: 2.07; 95% CI: 1.1592 - 3.7037; p < 0.001). Always confined dogs were twice more vaccinated than non-confined dogs. The results of the study showed that the vaccination coverage needs to be increased, the number of dog bites needs to be reduced, the number of non-confined dogs needs to be reduced and stray dog control strategies need to be implemented. The findings of this study showed very low vaccination coverage for dogs which is below the 70-80% target recommended for herd immunity by the world health organization.

microbiology↗

bioRxiv2020

First report of the sexual stage of the flax pathogen Mycosphaerella linicola in France and its impact on pasmo epidemiology

We performed a three-year field survey in France to characterize the dynamics of sexual reproduction in Mycosphaerella linicola, the causal agent of pasmo, during the interepidemic period. Cohorts of fruiting bodies were sampled from linseed straw during the autumn and winter and carefully observed, focusing on pseudothecia, asci and ascospores. A sequence of experimental steps corresponding to Kochs postulates confirmed in July 2014, for the first time in France and continental Europe, the widespread presence of the sexual stage of M. linicola in plant host tissues. The developmental dynamics of pseudothecia on straw, expressed as the change over time in the percentage of mature pseudothecia, was similar in all three years. Pseudothecia appeared in late summer, with peak maturity reached in October. A temporal shift, thought to be due to early autumn rainfall, was highlighted in one of the three years. These observations suggest that sexual reproduction plays a significant role in the epidemiology of pasmo in France. A resurgence of M. linicola infections in spring flax is thought to have occurred in recent years, due to the increase in the area under flax. The presence of the sexual stage of this pathogen probably increased the quantitative impact of residues of winter linseed (used for oil) and flax straw (left on the soil for retting and used for fibers) as an interepidemic brown bridge. This case study highlights how certain parts of a disease cycle, in this case the sexual phase, can become crucial due to changes in production conditions.

pathology↗

bioRxiv2020

Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco

COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.

genomics↗

bioRxiv2020

Elucidation of global and local epidemiology of Salmonella Enteritidis through multilevel genome typing

Salmonella enterica serovar Enteritidis is a major cause of foodborne Salmonella infections and outbreaks in humans. Effective surveillance and timely outbreak detection are essential for public health control. Multilevel genome typing (MGT) with multiple levels of resolution has been previously demonstrated as a promising tool for this purpose. In this study, we developed MGT with nine levels for S. Enteritidis and characterised the genomic epidemiology of S. Enteritidis in detail. We examined 26,670 publicly available S. Enteritidis genome sequences from isolates spanning 101 years from 86 countries to reveal their spatial and temporal distributions. Using the lower resolution MGT levels, globally prevalent and regionally restricted sequence types (STs) were identified; avian associated MGT4-STs were found that were common in human cases in the USA were identified; temporal trends were observed in the UK with MGT5-STs from 2014 to 2018, revealing both long lived endemic STs and the rapid expansion of new STs. Using MGT3 to MGT6, we identified MDR associated STs at various MGT levels, which improves precision of detection and global tracking of MDR clones. We also found that the majority of the global S. Enteritidis population fell within two predominant lineages, which had significantly different propensity of causing large scale outbreaks. An online open MGT database has been established for unified international surveillance of S. Enteritidis. We demonstrated that MGT provides a flexible and high-resolution genome typing tool for S. Enteritidis surveillance and outbreak detection. Impact statementSalmonella enterica serovar Enteritidis is a common foodborne pathogen that can cause large outbreaks. Surveillance and high-resolution typing are essential for outbreak prevention and control. Genome sequencing offers unprecedented power for these purposes and a standardised method or platform for the interpretation, comparison and communication of genomic typing data is highly desirable. In this work, we developed a genomic typing scheme called Multilevel Genome Typing (MGT) for S. Enteritidis. We analysed 26,670 publicly available genomes of S. Enteritidis using MGT. We characterised the geographic and temporal distribution of S. Enteritidis MGT types as well as their association with multidrug resistance (MDR) and virulence genes. A publicly available MGT database for S. Enteritidis was established, which has the potential facilitate the unified global public health surveillance for this pathogen. Data SummaryO_LIThe MGT database for S. Enteritidis is available at https://mgtdb.unsw.edu.au/enteritidis/. C_LIO_LIAll accession numbers of the public available genomes were available in the MGT database and Data Set S1, Tab 1. And there were no newly sequenced data in this study. C_LIO_LISupplementary material: Supplementary Fig. S1 to S7, supplementary methods and supporting results about the evaluation of potential repeat sequencing bias. C_LIO_LIData Set S1: Supporting tables of the main results. C_LIO_LIData Set S2. Supporting tables of the repeat sequencing bias evaluation by removing the potential repeat sequencing isolates. Note outbreak isolates may also be removed. C_LI

genomics↗

bioRxiv2020

Post-intervention Epidemiology of STH in Bangladesh: data to sustain the gains

IntroductionIn 2008, Bangladesh initiated Preventive Chemotherapy (PCT) for school-age children (SAC) through bi-annual school-based mass drug administration (MDA) to control Soil-Transmitted Helminth (STH) infections. In 2016, the Ministry of Health and Family Welfares Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact assessments with Children Without Worms (CWW) using standardized, population-based sampling to measure the post-intervention STH burden across all ages ([≥] 1 yr) for the three STH species. Methods & Principal FindingsThe Integrated Community-based Survey for Program Monitoring (ICSPM) was developed by CWW and was used to survey 12 districts in Bangladesh from 2017 - 2020. We combined the individual demographic and parasite-specific characteristics from 10 districts and linked them with the laboratory data for collective analysis. Our analysis identified district-specific epidemiologic findings, important for program decisions. Of the 17,874 enrolled individuals, 10,824 (61%) provided stool samples. Overall, the prevalence of any STH species was substantially reduced to 14% from 79.8% in 2005. The impact was similar across all ages. STH prevalence was below 10% in 10 districts collectively, but remained high in 4 districts, despite their high reported PCT coverage in previous years. Among all, Bhola district was unique because it was the only district with high Trichuris prevalence. ConclusionBangladesh successfully lowered STH prevalence across all ages despite targeting SAC only. Data from the survey indicate significant number of adults and pre-school age children (PSAC) were self-deworming with purchased pills. This may account for the flat impact curve across all ages. Overall prevalence varied across surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible service and ecological factors. Discrepancies in the impact between districts highlight the need for district-level data to evaluate program implementation after consistent high PCT coverage. Authors SummaryBangladesh government conducted school-based mass drug administration (MDA) for over 10 years to control soil-transmitted helminth (STH) infections. School-based evaluations of MDA indicate a reduction in STH burden among school-aged children (SAC). To further assess the impact on the community, Children Without Worms and the Ministry of Health and Family Welfares Program on Lymphatic Filariasis Elimination and STH (ELFSTH) initiated district-level community impact surveys in 12 districts. We share the results from the latter 10 districts here. Our analysis of 10,824 interviews and stool samples from 10 districts showed an estimated 14% of community members infected with at least one species of STH. This finding is substantially lower than the baseline STH prevalence (79.8%) estimated in 2005. Bangladeshs successful impact was achieved across all ages despite only treating SAC. Deworming source data showed significant numbers of adults and pre-school age children (PSAC) self-dewormed with locally purchased pills. Prevalence varied across the surveyed districts, with persistent high transmission in the northeastern districts and a district in the central flood zone, indicating possible ecological and service factors contributing to persistent infections. Discrepancies in the impact across districts highlights the need for sub-national level data to evaluate program performance fllowing consistent high intervention.

scientific communication and education↗

bioRxiv2020

MicrobeTrace: Retooling Molecular Epidemiology for Rapid Public Health Response

MotivationOutbreak investigations use data from interviews, healthcare providers, laboratories and surveillance systems. However, integrated use of data from multiple sources requires a patchwork of software that present challenges in usability, interoperability, confidentiality, and cost. Rapid integration, visualization and analysis of data from multiple sources can guide effective public health interventions. ResultsWe developed MicrobeTrace to facilitate rapid public health responses by overcoming barriers to data integration and exploration in molecular epidemiology. Using publicly available HIV sequences and other data, we demonstrate the analysis of viral genetic distance networks and introduce a novel approach to minimum spanning trees that simplifies results. We also illustrate the potential utility of MicrobeTrace in support of contact tracing by analyzing and displaying data from an outbreak of SARS-CoV-2 in South Korea in early 2020. Availability and ImplementationMicrobeTrace is a web-based, client-side, JavaScript application (https://microbetrace.cdc.gov) that runs in Chromium-based browsers and remains fully-operational without an internet connection. MicrobeTrace is developed and actively maintained by the Centers for Disease Control and Prevention. The source code is available at https://github.com/cdcgov/microbetrace. Contactells@cdc.gov

bioinformatics↗

bioRxiv2020

Genomic epidemiology and evolution of Escherichia coli in wild animals

Escherichia coli is a common bacterial species in the gastrointestinal tracts of warm-blooded animals and humans. Pathogenic and antimicrobial resistance in E. coli may emerge via host switching from animal reservoirs. Despite its potential clinical importance, knowledge of the population structure of commensal E. coli within wild hosts and the epidemiological links between E. coli in non-human hosts and E. coli in humans is still scarce. In this study, we analysed the whole genome sequencing data of a collection of 119 commensal E. coli recovered from the guts of 68 mammal and bird species in Mexico and Venezuela in the 1990s. We observed low concordance between the population structures of E. coli colonizing wild animals and the phylogeny, taxonomy and ecological and physiological attributes of the host species, with distantly related E. coli often colonizing the same or similar host species and distantly related host species often hosting closely related E. coli. We found no evidence for recent transmission of E. coli genomes from wild animals to either domesticated animals or humans. However, multiple livestock- and human-related virulence factor genes were present in E. coli of wild animals, including virulence factors characteristic for Shiga toxin-producing E. coli (STEC) and atypical enteropathogenic E. coli (aEPEC), where several isolates from wild hosts harboured the locus of enterocyte effacement (LEE) pathogenicity island. Moreover, E. coli in wild animal hosts often harboured known antibiotic resistance determinants, including against ciprofloxacin, aminoglycosides, tetracyclines and beta-lactams, with some determinants present in multiple, distantly related E. coli lineages colonizing very different host animals. We conclude that although the genome pools of E. coli colonizing wild animal and human gut are well separated, they share virulence and antibiotic resistance genes and E. coli underscoring that wild animals could serve as reservoirs for E. coli pathogenicity in human and livestock infections. ImportanceEscherichia coli is a clinically importance bacterial species implicated in human and livestock associated infections worldwide. The bacterium is known to reside in the guts of humans, livestock and wild animals. Although wild animals are recognized to serve as potential reservoirs for pathogenic E. coli strains, the knowledge of the population structure of E. coli in wild hosts is still scarce. In this study we used the fine resolution of whole genome sequencing to provide novel insights into the evolution of E. coli genomes within a broad range of wild animal species (including mammals and birds), the co-evolution of E. coli strains with their hosts and the genetics of pathogenicity of E. coli strains in wild hosts. Our results provide evidence for the clinical importance of wild animals as reservoirs for pathogenic strains and necessitate the inclusion of non-human hosts in the surveillance programs for E. coli infections.

microbiology↗

bioRxiv2020

COVID-19: Variant screening, an important step towards precision epidemiology

Precision epidemiology using genomic technologies allows for a more targeted approach to COVID-19 control and treatment at individual and population level, and is the urgent need of the day. It enables identification of patients who may be at higher risk than others to COVID-19-related mortality, due to their genetic architecture, or who might respond better to a COVID-19 treatment. The COVID-19 virus, similar to SARS-CoV, uses the ACE2 receptor for cell entry and employs the cellular serine protease TMPRSS2 for viral S protein priming. This study aspires to present a multi-omics view of how variations in the ACE2 and TMPRSS2 genes affect COVID-19 infection and disease progression in affected individuals. It reports, for both genes, several variant and gene expression analysis findings, through (i) comparison analysis over single nucleotide polymorphisms (SNPs), that may account for the difference of COVID-19 manifestations among global sub-populations; (ii) calculating prevalence of structural variations (copy number variations (CNVs) / insertions), amongst populations; and (iii) studying expression patterns stratified by gender and age, over all human tissues. This work is a good first step to be followed by additional studies and functional assays towards informed treatment decisions and improved control of the infection rate.

genomics↗

bioRxiv2020

CoxBase: an online platform for epidemiological surveillance, visualization, analysis and typing of Coxiella burnetii genomic sequence

Q (query) fever is an infectious zoonotic disease caused by the Gram-negative bacteria Coxiella burnetii. Although the disease has been studied since decades, it still represents a threat due to sporadic outbreaks across farms in Europe. The absence of a central platform for Coxiella typing data management in an important epidemiological gap which is relevant in the case of an outbreak. To fill this gap, we have designed and implemented an online, open-source, and, web-based platform called CoxBase (https://coxbase.q-gaps.de). This platform includes a database that holds genotyping information of more than 400 Coxiella isolates alongside metadata that annotates them. We have also implemented features for in silico genotyping of completely or minimally assembled Coxiella sequences using five different typing methods, querying existing isolates, visualization of isolates geodata via aggregation on a world map and submission of new isolates. We tested our in silico typing method on 50 Coxiella genomes downloaded from the RefSeq database and we successfully genotyped all except for cases where the sequence quality was poor. We identified new spacer sequences using our implementation of the MST in silico typing method, and established adaA gene phenotypes for all 50 genomes as well as their plasmid types.

bioinformatics↗

bioRxiv2020

Principled simulation of agent-based models in epidemiology

After more than a century of sustained work by mathematicians, biologists, epidemiologists, probabilists, and other experts, dynamic models have become a vital tool for understanding and describing epidemics and disease transmission systems. Such models fulfill a variety of crucial roles including data integration, estimation of disease burden, forecasting trends, counterfactual evaluation, and parameter estimation. These models often incorporate myriad details, from age and social structure to inform population mixing patterns, commuting and migration, and immunological dynamics, among others. This complexity can be daunting, so many researchers have turned to stochastic simulation using agent-based models. Developing agent-based models, however, can present formidable technical challenges. In particular, depending on how the model updates state, unwanted or even unnoticed approximations can be introduced into a simulation model. In this article, we present computational methods for approximating continuous time discrete event stochastic processes based on a discrete time step to speed up complicated simulations which also converges to the true process as the time step goes to zero. Our stochastic models is constructed via hazard functions, and only those hazards which are dependent on the state of other agents (such as infection) are approximated, whereas hazards governing dynamics internal to an agent (such as immune response) are simulated exactly. By partitioning hazards as being either dependent or internal, a generic algorithm can be presented which is applicable to many models of contagion processes, with natural areas of extension and optimization. Author summaryStochastic simulation of epidemics is crucial to a variety of tasks in public health, encompassing intervention evaluation, trend forecasting, and estimation of epidemic parameters, among others. In many situations, due to model complexity, time constraints, unavailability or unfamiliarity with existing software, or other reasons, agent-based models are used to simulate epidemic processes. However, many simulation algorithms are ad hoc, which may introduce unwanted or unnoticed approximations. We present a method to build approximate, agent-based models from mathematical descriptions of stochastic epidemic processes which will improve simulation speed and converge to exact simulation techniques in limiting cases. The simplicity and generality of our method should be widely applicable to various problems in mathematical epidemiology and its connection to other methods developed in chemical physics should inspire future work and elaboration.

ecology↗