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BACKGROUND: Following a one-health approach, we sought to determine reservoirs of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), other than Escherichia coli or Klebsiella pneumoniae complex species (i.e., low-abundant species), and their associated ESBL genes and plasmid-replicon profiles. METHODS: From 06/2017-05/2019, ESBL-PE isolates were recovered from clinical samples routinely collected at the University Hospital Basel (Basel, Switzerland), as well as from wastewater and foodstuffs collected monthly at predefined locations throughout the city of Basel. Whole-genome sequencing was performed for characterization of ESBL-PE isolates. RESULTS: Among 1634 isolates recovered, 114 (7%) belonged to 17 low-abundant ESBL-PE species. Seven species originated from more than one compartment, mainly from clinical and wastewater samples (6/17). Sixteen different ESBL genes were identified, with blaCTX-M-15 (27%), blaFONA-6 (23%) and blaSHV-12 (16%) being most frequent. The blaCTX-M-1 gene was the only ESBL gene recovered from all three compartments. Putative plasmids constituted 60% of ESBL gene-containing contigs, while chromosomes comprised 40%. Foodstuff isolates showed the highest proportion (91%, 41/45) of ESBL genes located on chromosomes, whereas wastewater isolates had the highest proportion (95%, 37/39) of putative plasmids. Multi-replicon combinations were identified in 81% of the isolates. Epidemiological links were found among some clinical and wastewater isolates. CONCLUSIONS: The dominance of blaCTX-M-15 among low-abundant ESBL-PE species supports its species-independent transmission potential beyond the E. coli and K. pneumoniae complex, and blaCTX-M-1 may be transmitted between strains recovered from different compartments. The substantial overlap between low-abundant ESBL-PE present in wastewater and clinical samples supports the utility of wastewater surveillance for antibiotic resistance monitoring.
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Persons living with HIV are known to be at increased risk of developing tuberculosis (TB) disease upon infection with Mycobacterium tuberculosis (Mtb). However, it has remained unclear how HIV co-infection affects subsequent Mtb transmission from these patients. Here, we customized a Bayesian phylodynamic framework to estimate the effects of HIV co-infection on the Mtb transmission dynamics from sequence data. We applied our model to four Mtb genomic datasets collected in sub-Saharan African countries with a generalized HIV epidemic. Our results confirm that HIV co-infection is a strong risk factor for developing active TB. Additionally, we demonstrate that HIV co-infection is associated with a reduced effective reproductive number for TB. Stratifying the population by CD4+ T-cell count yielded similar results, suggesting that, in this context, CD4+ T-cell count is not a better predictor of Mtb transmissibility than HIV infection status alone. Together, our genome-based analyses complement observational household contact studies, and more firmly establish the negative association between HIV co-infection and Mtb transmissibility.
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Coinfección , Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Humanos , África del Sur del Sahara/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/transmisión , Infecciones por VIH/epidemiología , Coinfección/microbiología , Coinfección/epidemiología , Tuberculosis/epidemiología , Tuberculosis/transmisión , Tuberculosis/microbiología , Masculino , Recuento de Linfocito CD4 , Femenino , Teorema de Bayes , Adulto , Factores de RiesgoRESUMEN
Wastewater-based epidemiology offers a complementary approach to clinical case-based surveillance of emergent diseases and can help identify regions with infected people to prioritize clinical surveillance strategies. However, tracking emergent diseases in wastewater requires reliance on novel testing assays with uncertain sensitivity and specificity. Limited pathogen shedding may cause detection to be below the limit of quantification or bordering the limit of detection. Here, we investigated how the definition of limit of detection for quantitative polymerase chain reaction (qPCR) impacts epidemiological insights during an mpox outbreak in Switzerland. 365 wastewater samples from three wastewater treatment plants in Switzerland from 9 March through 31 October 2022 were analyzed for mpox DNA using qPCR. We detected mpox DNA in 22% (79 of 365) wastewater samples based on a liberal definition of qPCR detection as any exponentially increasing fluorescence above the threshold. Based on a more restrictive definition as the lowest concentration at which there is 95% likelihood of detection, detection was 1% (5 of 365). The liberal definition shows high specificity (90%) and accuracy (78%), but moderate sensitivity (64%) when benchmarked against available clinical case reporting, which contrasts with higher specificity (98%) but lower sensitivity (10%) and accuracy (56%) of the 95% likelihood definition. Wastewater-based epidemiology applied to an emergent pathogen will require optimizing public health trade-offs between reporting data with high degrees of uncertainty and delaying communication and associated action. Information sharing with relevant public health stakeholders could couple early results with clear descriptions of uncertainty.Impact Statement: When a novel pathogen threatens to enter a community, wastewater-based epidemiology offers an opportunity to track its emergence and spread. However, rapid deployment of methods for to detect a novel pathogen may rely on assays with uncertain sensitivity and specificity. Benchmarking the detection of mpox DNA in Swiss wastewaters with reported clinical cases in 2022, we demonstrate how definitions of detection of a qPCR assay influence epidemiological insights from wastewater. The results highlight the need for information sharing between public health stakeholders that couple early insights from wastewater with descriptions of methodological uncertainty to optimize public health actions.
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The time-varying effective reproduction number Rt is a widely used indicator of transmission dynamics during infectious disease outbreaks. Timely estimates of Rt can be obtained from reported cases counted by their date of symptom onset, which is generally closer to the time of infection than the date of report. Case counts by date of symptom onset are typically obtained from line list data, however these data can have missing information and are subject to right truncation. Previous methods have addressed these problems independently by first imputing missing onset dates, then adjusting truncated case counts, and finally estimating the effective reproduction number. This stepwise approach makes it difficult to propagate uncertainty and can introduce subtle biases during real-time estimation due to the continued impact of assumptions made in previous steps. In this work, we integrate imputation, truncation adjustment, and Rt estimation into a single generative Bayesian model, allowing direct joint inference of case counts and Rt from line list data with missing symptom onset dates. We then use this framework to compare the performance of nowcasting approaches with different stepwise and generative components on synthetic line list data for multiple outbreak scenarios and across different epidemic phases. We find that under reporting delays realistic for hospitalization data (50% of reports delayed by more than a week), intermediate smoothing, as is common practice in stepwise approaches, can bias nowcasts of case counts and Rt, which is avoided in a joint generative approach due to shared regularization of all model components. On incomplete line list data, a fully generative approach enables the quantification of uncertainty due to missing onset dates without the need for an initial multiple imputation step. In a real-world comparison using hospitalization line list data from the COVID-19 pandemic in Switzerland, we observe the same qualitative differences between approaches. The generative modeling components developed in this work have been integrated and further extended in the R package epinowcast, providing a flexible and interpretable tool for real-time surveillance.
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Número Básico de Reproducción , Teorema de Bayes , COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/transmisión , Número Básico de Reproducción/estadística & datos numéricos , Brotes de Enfermedades/estadística & datos numéricos , Biología Computacional/métodos , SARS-CoV-2 , Simulación por ComputadorRESUMEN
Many different animal species are susceptible to SARS-CoV-2, including a few Canidae (domestic dog and raccoon dog). So far, only experimental evidence is available concerning SARS-CoV-2 infections in red foxes (Vulpes vulpes). This is the first report of SARS-CoV-2 RNA detection in a sample from a red fox. The RT-qPCR-positive fox was zoo-kept together with another fox and two bears in the Swiss Canton of Zurich. Combined material from a conjunctival and nasal swab collected for canine distemper virus diagnostics tested positive for SARS-CoV-2 RNA with Ct values of 36.9 (E gene assay) and 35.7 (RdRp gene assay). The sample was analysed for SARS-CoV-2 within a research project testing residual routine diagnostic samples from different animal species submitted between spring 2020 and December 2022 to improve knowledge on SARS-CoV-2 infections within different animal species and investigate their potential role in a One Health context. Within this project, 246 samples from 153 different animals from Swiss zoos and other wild animal species all tested SARS-CoV-2 RT-qPCR and/or serologically negative so far, except for the reported fox. The source of SARS-CoV-2 in the fox is unknown. The fox disappeared within the naturally structured enclosure, and the cadaver was not found. No further control measures were undertaken.
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Animales de Zoológico , COVID-19 , Zorros , ARN Viral , SARS-CoV-2 , Animales , Zorros/virología , COVID-19/diagnóstico , COVID-19/virología , COVID-19/veterinaria , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Animales de Zoológico/virología , ARN Viral/genética , ARN Viral/aislamiento & purificación , SuizaRESUMEN
INTRODUCTION: Influenza infections are challenging to monitor at the population level due to many mild and asymptomatic cases and similar symptoms to other common circulating respiratory diseases, including COVID-19. Methods for tracking cases outside of typical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviours. METHODS: We quantified influenza A and B virus loads from influent at Switzerland's three largest wastewater treatment plants, serving about 14% of the Swiss population (1.2 million individuals). We estimated trends in infection incidence and the effective reproductive number (Re) in these catchments during a 2021/22 epidemic and compared our estimates to typical influenza surveillance data. RESULTS: Wastewater data captured the same overall trends in infection incidence as laboratory-confirmed case data at the catchment level. However, the wastewater data were more sensitive in capturing a transient peak in incidence in December 2021 than the case data. The Re estimated from the wastewater data was roughly at or below the epidemic threshold of 1 during work-from-home measures in December 2021 but increased to at or above the epidemic threshold in two of the three catchments after the relaxation of these measures. The third catchment yielded qualitatively the same results but with wider confidence intervals. The confirmed case data at the catchment level yielded comparatively less precise R_e estimates before and during the work-from-home period, with confidence intervals that included one before and during the work-from-home period. DISCUSSION: Overall, we show that influenza RNA in wastewater can help monitor nationwide influenza transmission dynamics. Based on this research, we developed an online dashboard for ongoing wastewater-based influenza surveillance in Switzerland.
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COVID-19 , Gripe Humana , Humanos , Gripe Humana/epidemiología , Suiza/epidemiología , Aguas Residuales , ARNRESUMEN
During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent-something that is unknown at the time of sequencing-and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.IMPORTANCESwitzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses.
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COVID-19 , Genoma Viral , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/virología , COVID-19/diagnóstico , Humanos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/clasificación , Suiza/epidemiología , Genoma Viral/genética , Monitoreo Epidemiológico , Pandemias , FilogeniaRESUMEN
We estimate the basic reproductive number and case counts for 15 distinct Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, distributed across 11 populations (10 countries and one cruise ship), based solely on phylodynamic analyses of genomic data. Our results indicate that, prior to significant public health interventions, the reproductive numbers for 10 (out of 15) of these outbreaks are similar, with median posterior estimates ranging between 1.4 and 2.8. These estimates provide a view which is complementary to that provided by those based on traditional line listing data. The genomic-based view is arguably less susceptible to biases resulting from differences in testing protocols, testing intensity, and import of cases into the community of interest. In the analyses reported here, the genomic data primarily provide information regarding which samples belong to a particular outbreak. We observe that once these outbreaks are identified, the sampling dates carry the majority of the information regarding the reproductive number. Finally, we provide genome-based estimates of the cumulative number of infections for each outbreak. For 7 out of 11 of the populations studied, the number of confirmed cases is much bigger than the cumulative number of infections estimated from the sequence data, a possible explanation being the presence of unsequenced outbreaks in these populations.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Brotes de Enfermedades , Genómica , NavíosRESUMEN
Background: The involvement of non-human-to-human transmission of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute to their spread. Aim: We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city. Methods: Chicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing. Results: Among 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species. Escherichia coli and Serratia fonticola were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (p < 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with E. coli as predominant (17.6%). ESBL-producing Enterobacter cloacae was detected among different greens. Yet, ESBL-producing Klebsiella pneumoniae was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (p < 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-E. coli (33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (p = 0.122). Instead, differences were observed between regions of food production and countries (p < 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (p = 0.107). Conclusion: Our findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially E. coli, while greens are more prone to carry ESBL-K. pneumoniae and E. cloacae. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species.
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Despite recognition of the immediate impact of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) on human health, essential aspects of their molecular epidemiology remain under-investigated. This includes knowledge on the potential of a particular strain to persist in a host, mutational events during colonization, and the genetic diversity in individual patients over time. To investigate long-term genetic diversity of colonizing and infecting ESBL-Klebsiella pneumoniae species complex and ESBL-Escherichia coli in individual patients over time, we performed a ten-year longitudinal retrospective study and extracted clinical and microbiological data from electronic health records. In this investigation, 76 ESBL-K. pneumoniae species complex and 284 ESBL-E. coli isolates were recovered from 19 and 61 patients. Strain persistence was detected in all patients colonized with ESBL-K. pneumoniae species complex, and 83.6% of patients colonized with ESBL-E. coli. We frequently observed isolates of the same strain recovered from different body sites associated with either colonization or infection. Antimicrobial resistance genes, plasmid replicons, and whole ESBL-plasmids were shared between isolates regardless of chromosomal relatedness. Our study suggests that patients colonized with ESBL-producers may act as durable reservoirs for ongoing transmission of ESBLs, and that they are at prolonged risk of recurrent infection with colonizing strains.
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Infecciones por Escherichia coli , Infecciones por Klebsiella , Humanos , Escherichia coli/genética , Infecciones por Escherichia coli/microbiología , Estudios Retrospectivos , beta-Lactamasas/genética , Infecciones por Klebsiella/microbiología , Klebsiella , Klebsiella pneumoniae/genética , Variación Genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad MicrobianaRESUMEN
BackgroundThe earliest recognised infections by the SARS-CoV-2 Omicron variant (Pango lineage B.1.1.529) in Belgium and Switzerland suggested a connection to an international water polo tournament, held 12-14 November 2021 in Brno, Czechia.AimTo study the arrival and subsequent spread of the Omicron variant in Belgium and Switzerland, and understand the overall importance of this international sporting event on the number of infections in the two countries.MethodsWe performed intensive forward and backward contact tracing in both countries, supplemented by phylogenetic investigations using virus sequences of the suspected infection chain archived in public databases.ResultsThrough contact tracing, we identified two and one infected athletes of the Belgian and Swiss water polo teams, respectively, and subsequently also three athletes from Germany. In Belgium and Switzerland, four and three secondary infections, and three and one confirmed tertiary infections were identified. Phylogenetic investigation demonstrated that this sporting event played a role as the source of infection, but without a direct link with infections from South Africa and not as a superspreading event; the virus was found to already be circulating at that time in the countries involved.ConclusionThe SARS-CoV-2 Omicron variant started to circulate in Europe several weeks before its identification in South Africa on 24 November 2021. Accordingly, it can be assumed that travel restrictions are usually implemented too late to prevent the spread of newly detected SARS-CoV-2 variants to other regions. Phylogenetic analysis may modify the perception of an apparently clear result of intensive contact tracing.
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COVID-19 , Deportes Acuáticos , Humanos , SARS-CoV-2/genética , Bélgica/epidemiología , Suiza/epidemiología , República Checa , Filogenia , COVID-19/epidemiología , AlemaniaRESUMEN
The effective reproductive number Rt has taken a central role in the scientific, political, and public discussion during the COVID-19 pandemic, with numerous real-time estimates of this quantity routinely published. Disagreement between estimates can be substantial and may lead to confusion among decision-makers and the general public. In this work, we compare different estimates of the national-level effective reproductive number of COVID-19 in Germany in 2020 and 2021. We consider the agreement between estimates from the same method but published at different time points (within-method agreement) as well as retrospective agreement across eight different approaches (between-method agreement). Concerning the former, estimates from some methods are very stable over time and hardly subject to revisions, while others display considerable fluctuations. To evaluate between-method agreement, we reproduce the estimates generated by different groups using a variety of statistical approaches, standardizing analytical choices to assess how they contribute to the observed disagreement. These analytical choices include the data source, data pre-processing, assumed generation time distribution, statistical tuning parameters, and various delay distributions. We find that in practice, these auxiliary choices in the estimation of Rt may affect results at least as strongly as the selection of the statistical approach. They should thus be communicated transparently along with the estimates.
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COVID-19 , Humanos , COVID-19/epidemiología , Número Básico de Reproducción , Pandemias , Estudios Retrospectivos , Alemania/epidemiologíaRESUMEN
Several total-evidence dating studies under the fossilized birth-death (FBD) model have produced very old age estimates, which are not supported by the fossil record. This phenomenon has been termed "deep root attraction (DRA)." For two specific data sets, involving divergence time estimation for the early radiations of ants, bees, and wasps (Hymenoptera) and of placental mammals (Eutheria), it has been shown that the DRA effect can be greatly reduced by accommodating the fact that extant species in these trees have been sampled to maximize diversity, so-called diversified sampling. Unfortunately, current methods to accommodate diversified sampling only consider the extreme case where it is possible to identify a cut-off time such that all splits occurring before this time are represented in the sampled tree but none of the younger splits. In reality, the sampling bias is rarely this extreme and may be difficult to model properly. Similar modeling challenges apply to the sampling of the fossil record. This raises the question of whether it is possible to find dating methods that are more robust to sampling biases. Here, we show that the skyline FBD (SFBD) process, where the diversification and fossil-sampling rates can vary over time in a piecewise fashion, provides age estimates that are more robust to inadequacies in the modeling of the sampling process and less sensitive to DRA effects. In the SFBD model we consider, rates in different time intervals are either considered to be independent and identically distributed or assumed to be autocorrelated following an Ornstein-Uhlenbeck (OU) process. Through simulations and reanalyses of Hymenoptera and Eutheria data, we show that both variants of the SFBD model unify age estimates under random and diversified sampling assumptions. The SFBD model can resolve DRA by absorbing the deviations from the sampling assumptions into the inferred dynamics of the diversification process over time. Although this means that the inferred diversification dynamics must be interpreted with caution, taking sampling biases into account, we conclude that the SFBD model represents the most robust approach currently available for addressing DRA in total-evidence dating.
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Hormigas , Placenta , Femenino , Embarazo , Animales , Filogenia , Tiempo , Euterios , FósilesRESUMEN
BACKGROUND: Accurate estimation of the effective reproductive number ([Formula: see text]) of epidemic outbreaks is of central relevance to public health policy and decision making. We present estimateR, an R package for the estimation of the reproductive number through time from delayed observations of infection events. Such delayed observations include confirmed cases, hospitalizations or deaths. The package implements the methodology of Huisman et al. but modularizes the [Formula: see text] estimation procedure to allow easy implementation of new alternatives to the currently available methods. Users can tailor their analyses according to their particular use case by choosing among implemented options. RESULTS: The estimateR R package allows users to estimate the effective reproductive number of an epidemic outbreak based on observed cases, hospitalization, death or any other type of event documenting past infections, in a fast and timely fashion. We validated the implementation with a simulation study: estimateR yielded estimates comparable to alternative publicly available methods while being around two orders of magnitude faster. We then applied estimateR to empirical case-confirmation incidence data for COVID-19 in nine countries and for dengue fever in Brazil; in parallel, estimateR is already being applied (i) to SARS-CoV-2 measurements in wastewater data and (ii) to study influenza transmission based on wastewater and clinical data in other studies. In summary, this R package provides a fast and flexible implementation to estimate the effective reproductive number for various diseases and datasets. CONCLUSIONS: The estimateR R package is a modular and extendable tool designed for outbreak surveillance and retrospective outbreak investigation. It extends the method developed for COVID-19 by Huisman et al. and makes it available for a variety of pathogens, outbreak scenarios, and observation types. Estimates obtained with estimateR can be interpreted directly or used to inform more complex epidemic models (e.g. for forecasting) on the value of [Formula: see text].
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Número Básico de Reproducción , Estudios Retrospectivos , Aguas ResidualesRESUMEN
BACKGROUND: Recent epidemic outbreaks such as the SARS-CoV-2 pandemic and the mpox outbreak in 2022 have demonstrated the value of genomic sequencing data for tracking the origin and spread of pathogens. Laboratories around the globe generated new sequences at unprecedented speed and volume and bioinformaticians developed new tools and dashboards to analyze this wealth of data. However, a major challenge that remains is the lack of simple and efficient approaches for accessing and processing sequencing data. RESULTS: The Lightweight API for Sequences (LAPIS) facilitates rapid retrieval and analysis of genomic sequencing data through a REST API. It supports complex mutation- and metadata-based queries and can perform aggregation operations on massive datasets. LAPIS is optimized for typical questions relevant to genomic epidemiology. Using a newly-developed in-memory database engine, it has a high speed and throughput: between 25 January and 4 February 2023, the SARS-CoV-2 instance of LAPIS, which contains 14.5 million sequences, processed over 20 million requests with a mean response time of 411 ms and a median response time of 1 ms. LAPIS is the core engine behind our dashboards on genspectrum.org and we currently maintain public LAPIS instances for SARS-CoV-2 and mpox. CONCLUSIONS: Powered by an optimized database engine and available through a web API, LAPIS enhances the accessibility of genomic sequencing data. It is designed to serve as a common backend for dashboards and analyses with the potential to be integrated into common database platforms such as GenBank.
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COVID-19 , Mpox , Humanos , SARS-CoV-2/genética , Genoma , GenómicaRESUMEN
Background: The contribution of community and hospital sources to the transmission of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) remains elusive. Aim: To investigate the extent of community dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel. Methods: Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites, n = 17) or community and hospital wastewater (mixed sites, n = 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification. Results: Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates, Escherichia coli (85%, 1,140/1,334) and Klebsiella pneumoniae (11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with E. coli consistently predominating. The proportion of K. pneumoniae isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of E. coli was higher in samples from urban sites (p = 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 102 vs. 1.6 × 102 CFU/mL). E. coli-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21). Conclusion: ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent.
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In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Tanzanía/epidemiología , Tuberculosis/epidemiología , Genotipo , VirulenciaRESUMEN
Multidrug-resistant tuberculosis (MDR-TB) is among the most frequent causes of death due to antimicrobial resistance. Although only 3% of global TB cases are MDR, geographical hotspots with up to 40% of MDR-TB have been observed in countries of the former Soviet Union. While the quality of TB control and patient-related factors are known contributors to such hotspots, the role of the pathogen remains unclear. Here we show that in the country of Georgia, a known hotspot of MDR-TB, MDR Mycobacterium tuberculosis strains of lineage 4 (L4) transmit less than their drug-susceptible counterparts, whereas most MDR strains of L2 suffer no such defect. Our findings further indicate that the high transmission fitness of these L2 strains results from epistatic interactions between the rifampicin resistance-conferring mutation RpoB S450L, compensatory mutations in the RNA polymerase, and other pre-existing genetic features of L2/Beijing clones that circulate in Georgia. We conclude that the transmission fitness of MDR M. tuberculosis strains is heterogeneous, but can be as high as drug-susceptible forms, and that such highly drug-resistant and transmissible strains contribute to the emergence and maintenance of hotspots of MDR-TB. As these strains successfully overcome the metabolic burden of drug resistance, and given the ongoing rollout of new treatment regimens against MDR-TB, proper surveillance should be implemented to prevent these strains from acquiring resistance to the additional drugs.
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Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Mutación , Rifampin/farmacología , Rifampin/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
In 2013 to 2017, avian influenza A(H7N9) virus has caused five severe epidemic waves of human infections in China. The role of live bird markets (LBMs) in the transmission dynamics of H7N9 remains unclear. Using a Bayesian phylodynamic approach, we shed light on past H7N9 transmission events at the human-LBM interface that were not directly observed using case surveillance data-based approaches. Our results reveal concurrent circulation of H7N9 lineages in Yangtze and Pearl River Delta regions, with evidence of local transmission during each wave. Our results indicate that H7N9 circulated in humans and LBMs for weeks to months before being first detected. Our findings support the seasonality of H7N9 transmission and suggest a high number of underreported infections, particularly in LBMs. We provide evidence for differences in virus transmissibility between low and highly pathogenic H7N9. We demonstrate a regional spatial structure for the spread of H7N9 among LBMs, highlighting the importance of further investigating the role of local live poultry trade in virus transmission. Our results provide estimates of avian influenza virus (AIV) transmission at the LBM level, providing a unique opportunity to better prepare surveillance plans at LBMs for response to future AIV epidemics.