Disentangling outbreaks using whole-genome sequencing: concurrent multistate outbreaks of Salmonella Kottbus in Germany, 2017

Abstract In June 2017, an outbreak of Salmonella Kottbus infection was suspected in Germany. We investigated the outbreak with whole-genome sequencing (WGS) and a case–control study. Forty-six isolates from 69 cases were subtyped. Three WGS clusters were identified: cluster 1 (n = 36), cluster 2 (n = 5) and cluster 3 (n = 3). Compared to controls, cluster 1 cases more frequently consumed raw smoked ham (odds ratio (OR) 10, 95% confidence interval (CI) 1.2–88) bought at supermarket chain X (OR 36, 95% CI 4–356; 9/10 consumed ham Y). All four cluster 2 cases interviewed had consumed quail eggs. Timely WGS was invaluable in distinguishing concurrent outbreaks of a rare Salmonella serotype.

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OP38 Developing a Cost-Effective Genomic Biomarker of Cancer Risk in Patients with Ulcerative Colitis using Low-Pass Whole Genome Sequencing of Unselected Endoscopic Biopsies: A Case-Control Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.037 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S035-S036

Author(s):

I Al Bakir ◽

K Curtius ◽

K Smith ◽

M Kopczynska ◽

M Moorghen ◽

...

Keyword(s):

Ulcerative Colitis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Copy Number ◽

Case Control Study ◽

Case Control ◽

Whole Genome ◽

Low Pass ◽

And Control ◽

Control Study

Abstract Background Patients with ulcerative colitis (UC) are enrolled into surveillance programs for the early detection of colorectal cancer (CRC). However, most patients under surveillance are low-risk and never progress to CRC, while a significant proportion of CRCs in UC form without a preceding confirmed diagnosis of dysplasia. High resolution chromosomal copy-number alteration (CNA) analysis of unselected formalin-fixed paraffin embedded biopsies taken at surveillance colonoscopies using low pass whole genome sequencing (lpWGS) offers an appealing approach to CRC stratification. Methods We conducted a retrospective case-control study to compare the CNA burden in four unselected non-neoplastic left-sided colorectal biopsies from patients with E2/E3 UC derived 1–5 years prior to HGD/CRC detection (cases), with that of biopsies from patients who subsequently remained HGD/CRC-free for at least 5 years (controls). The two patient groups were matched by age, gender, duration of IBD and PSC status. lpWGS was performed using a standardised pipeline for epithelial enrichment, DNA extraction, library preparation, next generation sequencing and bioinformatic analysis. Results 476 biopsies, derived from 42 cases and 77 controls, were analysed. Nearly 80% of patients had a detectable CNA in at least one of their biopsies, with the maximal CNA burden in a typical biopsy involving a median 1.1% of that biopsy’s genome. The CNA burden was significantly greater in the rectum compared to the sigmoid colon and descending colon. The most common CNA events were losses of between 1–30 megabases involving the sub-telomeric regions of chromosomes 5–9 and 22, which were found in similar proportion in both case and control biopsies. However, losses extending beyond sub-telomeric regions, as well as copy number gains, were found more frequently in cases biopsies (p<0.0001). The most discriminating CNA event was the presence of such a loss extending beyond subtelomeric regions in any of the patient’s four biopsies, with a high specificity exceeding 0.95 (see Kaplan-Meier plot). ROC analysis demonstrates that lpWGS output has a fair level of accuracy at predicting future HGD/CRC risk (AUC 0.73). Conclusion We identified multiple biopsies, predominantly in cases, with a surprisingly marked CNA burden involving over 10% of the genome, highlighting the fluid phenotype-genotype relationship. Non-dysplastic colitic epithelium can bear a significant burden of CNAs and maintain phenotypic stability for years without neoplastic transformation. Remarkably, by analysing the CNA burden of only four random biopsies, derived from less than 0.05% of the colonic surface area, we can significantly discriminate between case and control cohorts.

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Investigating locally relevant risk factors forCampylobacterinfection in Australia: protocol for a case–control study and genomic analysis

BMJ Open ◽

10.1136/bmjopen-2018-026630 ◽

2018 ◽

Vol 8 (12) ◽

pp. e026630 ◽

Cited By ~ 5

Author(s):

Liana Varrone ◽

Russell J Stafford ◽

Kim Lilly ◽

Linda Selvey ◽

Kathryn Glass ◽

...

Keyword(s):

Risk Factors ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Case Control Study ◽

Geographical Area ◽

Companion Animals ◽

Case Control ◽

Whole Genome ◽

Source Attribution ◽

Control Study

IntroductionThe CampySource project aims to identify risk factors for humanCampylobacterinfection in Australia. We will investigate locally relevant risk factors and those significant in international studies in a case–control study. Case isolates and contemporaneous isolates from food and animal sources will be sequenced to conduct source attribution modelling, and findings will be combined with the case–control study in a source-assigned analysis.Methods and analysisThe case–control study will include 1200 participants (600 cases and 600 controls) across three regions in Australia. Cases will be recruited from campylobacteriosis notifications to health departments. Only those with a pure and viableCampylobacterisolate will be eligible for selection to allow for whole genome sequencing of isolates. Controls will be recruited from notified cases of influenza, frequency matched by sex, age group and geographical area of residence. All participants will be interviewed by trained telephone interviewers using a piloted questionnaire.We will collectCampylobacterisolates from retail meats and companion animals (specifically dogs), and all food, animal and human isolates will undergo whole genome sequencing. We will use sequence data to estimate the proportion of human infections that can be attributed to animal and food reservoirs (source attribution modelling), and to identify spatial clusters and temporal trends. Source-assigned analysis of the case–control study data will also be conducted where cases are grouped according to attributed sources.Ethics and disseminationHuman and animal ethics have been approved. Genomic data will be published in online archives accompanied by basic metadata. We anticipate several publications to come from this study.

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Whole-genome sequencing combined with a case-control study of an outbreak of staphylococcal food-poisoning

Epidemiology and Infection ◽

10.1017/s0950268820001132 ◽

2020 ◽

pp. 1-16

Author(s):

Ae Kyung Park ◽

Jungsun Park ◽

Eunkyung Shin ◽

Soojin Kim ◽

Hyun Ju Jung ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Case Control Study ◽

Food Poisoning ◽

Case Control ◽

Whole Genome ◽

Control Study

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Investigation of a staphylococcal food poisoning outbreak combining case–control, traditional typing and whole genome sequencing methods, Luxembourg, June 2014

Eurosurveillance ◽

10.2807/1560-7917.es.2015.20.45.30059 ◽

2015 ◽

Vol 20 (45) ◽

Cited By ~ 17

Author(s):

Joël Mossong ◽

Frédéric Decruyenaere ◽

Gilbert Moris ◽

Catherine Ragimbeau ◽

Christophe M. Olinger ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Case Control Study ◽

Food Poisoning ◽

Case Control ◽

Sequence Type ◽

Cold Chain ◽

Whole Genome ◽

Equine Sports ◽

Control Study

In June 2014, a staphylococcal food poisoning outbreak occurred at an international equine sports event in Luxembourg requiring the hospitalisation of 31 persons. We conducted a microbiological investigation of patients and buffet items, a case–control study and a carriage study of catering staff. Isolates of Staphylococcus aureus from patients, food and catering staff were characterised and compared using traditional typing methods and whole genome sequencing. Genotypically identical strains (sequence type ST8, spa-type t024, MLVA-type 4698, enterotoxin A FRI100) were isolated in 10 patients, shiitake mushrooms, cured ham, and in three members of staff. The case–control study strongly suggested pasta salad with pesto as the vehicle of infection (p<0.001), but this food item could not be tested, because there were no leftovers. Additional enterotoxigenic strains genetically unrelated to the outbreak strain were found in four members of staff. Non-enterotoxigenic strains with livestock-associated sequence type ST398 were isolated from three food items and two members of staff. The main cause of the outbreak is likely to have been not maintaining the cold chain after food preparation. Whole genome sequencing resulted in phylogenetic clustering which concurred with traditional typing while simultaneously characterising virulence and resistance traits.

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Plasma acylcarnitines and risk of lower-extremity functional impairment in older adults: a nested case–control study

Scientific Reports ◽

10.1038/s41598-021-82912-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Francisco Félix Caballero ◽

Ellen A. Struijk ◽

Alberto Lana ◽

Antonio Buño ◽

Fernando Rodríguez-Artalejo ◽

...

Keyword(s):

Older Adults ◽

Confidence Interval ◽

Lower Extremity ◽

Functional Impairment ◽

Odds Ratio ◽

Case Control Study ◽

Case Control ◽

Community Dwelling ◽

Control Study ◽

Long Chain

AbstractElevated concentrations of acylcarnitines have been associated with higher risk of obesity, type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the association between L-carnitine and acylcarnitine profiles, and 2-year risk of incident lower-extremity functional impairment (LEFI). This case–control study is nested in the Seniors-ENRICA cohort of community-dwelling older adults, which included 43 incident cases of LEFI and 86 age- and sex- matched controls. LEFI was assessed with the Short Physical Performance Battery. Plasma L-carnitine and 28 acylcarnitine species were measured. After adjusting for potential confounders, medium-chain acylcarnitines levels were associated with 2-year incidence of LEFI [odds ratio per 1-SD increase: 1.69; 95% confidence interval: 1.08, 2.64; p = 0.02]. Similar results were observed for long-chain acylcarnitines [odds ratio per 1-SD increase: 1.70; 95% confidence interval: 1.03, 2.80; p = 0.04]. Stratified analyses showed a stronger association between medium- and long-chain acylcarnitines and incidence of LEFI among those with body mass index and energy intake below the median value. In conclusion, higher plasma concentrations of medium- and long-chain acylcarnitines were associated with higher risk of LEFI. Given the role of these molecules on mitochondrial transport of fatty acids, our results suggest that bioenergetics dysbalance contributes to LEFI.

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Parental risk factors for congenital diaphragmatic hernia – a large German case-control study

BMC Pediatrics ◽

10.1186/s12887-021-02748-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Felicitas Schulz ◽

Ekkehart Jenetzky ◽

Nadine Zwink ◽

Charlotte Bendixen ◽

Florian Kipfmueller ◽

...

Keyword(s):

Risk Factors ◽

Confidence Interval ◽

Environmental Risk ◽

Odds Ratio ◽

Alcohol Intake ◽

Case Control Study ◽

Case Control ◽

Parental Risk Factors ◽

Healthy Control ◽

Control Study

Abstract Background Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns. Methods The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one. Results Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101–2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330–3.229, p = 0.001). Conclusion Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.

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Abstract WP369: Long Sleep Duration as a Risk Factor for Intracerebral Hemorrhage: a Nationwide, Multicenter Case-control Study

Stroke ◽

10.1161/str.47.suppl_1.wp369 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Tae Jung Kim ◽

Chi Kyung Kim ◽

Yerim Kim ◽

Han-Gil Jeong ◽

Kiwoong Nam ◽

...

Keyword(s):

Risk Factor ◽

Confidence Interval ◽

Intracerebral Hemorrhage ◽

Sleep Duration ◽

Odds Ratio ◽

Case Control Study ◽

Case Control ◽

Stroke Incidence ◽

Long Sleep ◽

Control Study

Introduction: Sleep duration has been regarded as a potential risk factor for cardiovascular disease and stroke. Short sleep duration is linked with higher stroke incidence, and mortality. Moreover, and paradoxically, long sleep duration is also reported to be positively associated with stroke incidence. However, the impact of sleep duration on the intracerebral hemorrhage (ICH) risk remains unclear. Hypothesis: We assessed the relationship between sleep duration and the risk of ICH. Methods: We performed a nationwide, multicenter matched case-control study to investigate the risk factors for hemorrhagic stroke, using patients from 33 hospitals in Korea. We enrolled a total of 490 patients with ICH and 980 age- and sex-matched controls. We obtained information regarding sleep, sociodemographic factors, lifestyle, and medical history before ICH onset, using qualified structured questionnaires. Sleep duration was categorized as ≤5, 6, 7, 8, and ≥9 hours. We chose sleep duration of 7 h as the reference duration. Results: The included patients were mostly male (58.2%) with a mean age of 57 years. The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). Compared to 7 h, long sleep duration participants tended to be older, be more hypertensive, and be more likely to have blue collar jobs, lower education levels, and poorer marital status (i.e., unmarried or divorced/separated). After controlling for confounding factors, we found that longer sleep duration was independently associated with the risk of ICH in a dose-response manner (8 h: Odds ratio, 1.44; confidence interval, 1.01-2.07; ≥9 h: Odds ratio, 2.60; confidence interval, 1.50–4.49). Conclusions: In conclusion, our study suggested that long sleep duration is positively related to ICH risk in a dose-dependent manner. In this context, our data might suggest that sleep duration is a modifiable risk factor for ICH.

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Adjacent-Level Ossification Development in Single-Level Standalone Anterior Cervical Discectomy and Fusion Versus Anterior Cervical Discectomy and Fusion With Plate

Global Spine Journal ◽

10.1177/2192568220902749 ◽

2020 ◽

pp. 219256822090274

Author(s):

Christopher Huang ◽

Ralph Mobbs ◽

Michael Selby ◽

Kevin Phan ◽

Prashanth Rao

Keyword(s):

Confidence Interval ◽

Odds Ratio ◽

Case Control Study ◽

Case Control ◽

Anterior Cervical Discectomy ◽

Adjacent Level ◽

Retrospective Case ◽

Cervical Discectomy ◽

Surgical Data ◽

Control Study

Study Design: Retrospective case control study. Objectives: Adjacent-level ossification development (ALOD) is a distinct form of adjacent segmental degeneration that has been recognized to occur after anterior cervical discectomy and fusion (ACDF). It is unclear whether ACDF with plate versus standalone has an effect on rates of ALOD. This retrospective case-control study aims to assess the rate of ALOD in a large series of patients undergoing ACDF with and without plate and factors causing ALOD. Methods: Data was collected for patients undergoing ACDF from January 2009 to July 2016. Data collected was from multiple centers and included demographic data, surgical data, radiological imaging at time of surgery, and serial follow-up imaging. The radiology for ALOD was independently reviewed. Cohorts were divided into ACDF with plate (Group P = plate) and ACDF without plate (Groups S = standalone) and outcomes were compared. Results: There were 260 patients with 138 (53%) in Group P and 122 (47%) in Group S. ALOD was observed in 15.3% of patients overall, 29% in group P and 2.8% in group S ( P < .001). Following multivariate adjustment, statistically significant association was found between use of plate and ALOD (odds ratio = 12.8, 95% confidence interval = 3.52-45.45, P < .001). Plate-to-disc distance <5 mm was significantly associated with ALOD (odds ratio = 13.5, 95% confidence interval = 3.83-47.62, P < .001). Conclusion: The use of anterior plate with ACDF was associated with ALOD. Plate-to-disc distance <5 mm was significantly associated with ALOD even after adjustment for confounding factors. We conclude utilization of standalone cages or cages with plate with more than 5 mm distance from adjacent disc to minimize ALOD.

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Current status of eye disorders caused by docetaxel administration every 3 weeks: A case-control study in Japanese patients

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219868761 ◽

2019 ◽

Vol 26 (3) ◽

pp. 655-665 ◽

Cited By ~ 3

Author(s):

Yusuke Noguchi ◽

Yugo Kawashima ◽

Megumi Maruyama ◽

Hiroko Kawara ◽

Yoko Tokuyama ◽

...

Keyword(s):

Visual Acuity ◽

Confidence Interval ◽

Odds Ratio ◽

Case Control Study ◽

Japanese Patients ◽

Case Control ◽

Current Status ◽

Eye Drops ◽

Eye Disorders ◽

Control Study

Purpose Docetaxel is known to cause eye disorders. In this study, current status of eye disorders caused by docetaxel administration every 3 weeks in Japanese patients was examined. Methods This case-control study targeted patients who were newly administered docetaxel at the Kyoto Okamoto Memorial Hospital between 1 July 2015 and 30 June 2018. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder. Results Of the 89 subjects, 7 (7.9%) had eye disorders. The symptoms were watering eyes (7.9%), a stye and eye discharge (2.2% each), corneal and conjunctival disorder, visual acuity reduction, and blepharedema (1.1% each). Four patients who presented with watering eyes, eye discharge, or corneal and conjunctival disorder showed improvement with the use of eye drops such as artificial tears. Two patients who presented with a stye showed improvement with the use of oral cefcapene. One patient with mild symptoms showed spontaneous improvement. However, one patient had irreversible visual acuity reduction. The multivariate logistic regression analysis revealed that a cumulative docetaxel dose of ≥300 mg/m2 (odds ratio: 15.50, 95% confidence interval: 1.37–175.00, p = 0.027) and concomitant cyclophosphamide use (odds ratio: 13.20, 95% confidence interval: 1.13–153.00, p = 0.039) were significant risk factors associated with eye disorders. Conclusion In conclusion, it was determined that docetaxel-related eye disorders might be influenced by the cumulative dose of docetaxel and concomitant cyclophosphamide use. In addition, relatively mild symptoms improved with medication.

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α+-thalassemia protects African children from severe malaria

Blood ◽

10.1182/blood-2003-11-4090 ◽

2004 ◽

Vol 104 (7) ◽

pp. 2003-2006 ◽

Cited By ~ 87

Author(s):

Frank P. Mockenhaupt ◽

Stephan Ehrhardt ◽

Sabine Gellert ◽

Rowland N. Otchwemah ◽

Ekkehart Dietz ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Natural Selection ◽

Confidence Interval ◽

Severe Malaria ◽

High Frequency ◽

Odds Ratio ◽

Case Control Study ◽

Case Control ◽

Control Study ◽

Selection Of

Abstract The high frequency of α+-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, α+-thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous α+-thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients with parasitemic controls (adjusted OR in children < 5 years of age, 0.52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of α+-thalassemia in Africa due to protection from severe malaria.

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