In early May 2022, a global outbreak of mpox started among persons without travel history to regions known to be enzootic for monkeypox virus (MPXV). On 8 August 2022, the Netherlands reported its... Show moreIn early May 2022, a global outbreak of mpox started among persons without travel history to regions known to be enzootic for monkeypox virus (MPXV). On 8 August 2022, the Netherlands reported its 1,000th mpox case, representing a cumulative incidence of 55 per million population, one of the highest cumulative incidences worldwide. We describe characteristics of the first 1,000 mpox cases in the Netherlands, reported between 20 May and 8 August 2022, within the context of the public health response. These cases were pre-dominantly men who have sex with men aged 31-45 years. The vast majority of infections were acquired through sexual contact with casual partners in pri-vate or recreational settings including LGBTQIA+ ven-ues in the Netherlands. This indicates that, although some larger upsurges occurred from point-source and/or travel-related events, the outbreak was mainly characterised by sustained transmission within the Netherlands. In addition, we estimated the protective effect of first-generation smallpox vaccine against moderate/severe mpox and found a vaccine effective-ness of 58% (95% CI: 17-78%), suggesting moderate protection against moderate/severe mpox symptoms on top of any possible protection by this vaccine against MPXV infection and disease. Communication with and supporting the at-risk population in following mitigation measures remains essential. Show less
During infection, Salmonella hijacks essential host signaling pathways. These molecular manipulations disrupt cellular integrity and may induce oncogenic transformation. Systemic S. Typhi... Show moreDuring infection, Salmonella hijacks essential host signaling pathways. These molecular manipulations disrupt cellular integrity and may induce oncogenic transformation. Systemic S. Typhi infections are linked to gallbladder cancer, whereas severe non-typhoidal Salmonella (NTS) infections are associated with colon cancer (CC). These diagnosed infections, however, represent only a small fraction of all NTS infections as many infections are mild and go unnoticed. To assess the overall impact of NTS infections, we performed a retrospective serological study on NTS exposure in patients with CC. The magnitude of exposure to NTS, as measured by serum antibody titer, is significantly positively associated with CC. Repetitively infecting mice with low NTS exposure showed similar accelerated tumor growth to that observed after high NTS exposure. At the cellular level, NTS preferably infects (pre-)transformed cells, and each infection round exponentially increases the rate of transformed cells. Thus, repetitive exposure to NTS associates with CC risk and accelerates tumor growth. Show less
Miura, F.; Ewijk, C.E. van; Backer, J.A.; Xiridou, M.; Franz, E.; Coul, E.O. de; ... ; Wallinga, J. 2022
In May 2022, monkeypox outbreaks have been reported in countries not endemic for monkeypox. We estimated the monkeypox incubation period, using reported exposure and symptom-onset times for 18... Show moreIn May 2022, monkeypox outbreaks have been reported in countries not endemic for monkeypox. We estimated the monkeypox incubation period, using reported exposure and symptom-onset times for 18 cases detected and confirmed in the Netherlands up to 31 May 2022. Mean incubation period was 8.5 days (5th-95th percentiles: 4.2-17.3), underpinning the current recommendation to monitor or isolate/quarantine case contacts for 21 days. However, as the incubation period may differ between different transmission routes, further epidemiological investigations are needed. Show less
Background: Gut colonisation by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is a risk factor for developing overt infection. The gut microbiome can provide colonisation... Show moreBackground: Gut colonisation by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is a risk factor for developing overt infection. The gut microbiome can provide colonisation resistance against enteropathogens, but it remains unclear whether it confers resistance against ESBL-producing E coli. We aimed to identify a potential role of the microbiome in controlling colonisation by this antibiotic-resistant bacterium.Methods: For this matched case-control study, we used faeces from 2751 individuals in a Dutch cross-sectional population study (PIENTER-3) to culture ESBL-producing bacteria. Of these, we selected 49 samples that were positive for an ESBL-producing E coli (ESBL-positive) and negative for several variables known to affect microbiome composition. These samples were matched 1:1 to ESBL-negative samples on the basis of individuals' age, sex, having been abroad or not in the past 6 months, and ethnicity. Shotgun metagenomic sequencing was done and taxonomic species composition and functional annotations (ie, microbial metabolism and carbohydrate-active enzymes) were determined. Targeted quantitative metabolic profiling (proton nuclear magnetic resonance spectroscopy) was done to investigate metabolomic profiles and combinations of univariate (t test and Wilcoxon test), multivariate (principal coordinates analysis, permutational multivariate analysis of variance, and partial least-squares discriminant analysis) and machine-learning approaches (least absolute shrinkage and selection operator and random forests) were used to analyse all the molecular data.Findings: No differences in diversity parameters or in relative abundance were observed between ESBL-positive and ESBL-negative groups based on bacterial species-level composition. Machine-learning approaches using microbiota composition did not accurately predict ESBL status (area under the receiver operating characteristic curve [AUROC]=0.41) when using either microbiota composition or any of the functional profiles. The metabolome also did not differ between ESBL groups, as assessed by various methods including random forest (AUROC=0- 61).Interpretation: By combining multiomics and machine-learning approaches, we conclude that asymptomatic gut carriage of ESBL-producing E. coli is not associated with an altered microbiome composition or function. This finding might suggest that microbiome-mediated colonisation resistance against ESBL-producing E, coli is not as relevant as it is against other enteropathogens and antibiotic-resistant bacteria. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. Show less
Duijster, J.W.; Franz, E.; Neefjes, J.; Mughini-Gras, L. 2021
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and... Show moreThe oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships. Show less
Duijster, J.W.; Hansen, J.V.; Franz, E.; Neefjes, J.J.C.; Frisch, M.; Mughini-Gras, L.; Ethelberg, S. 2021
Laboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with... Show moreLaboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994-2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC >= 1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88-1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC >= 1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03-1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48-2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notified Salmonella infections do not contribute significantly to CC risk in the studied population. Show less
Duijster, J.; Mughini-Gras, L.; Neefjes, J.; Franz, E. 2021
Objectives While colon cancer (CC) risk is associated with several lifestyle-related factors, including physical inactivity, smoking and diet, the contribution of occupation to CC morbidity remains... Show moreObjectives While colon cancer (CC) risk is associated with several lifestyle-related factors, including physical inactivity, smoking and diet, the contribution of occupation to CC morbidity remains largely unclear. Growing evidence indicates that gastrointestinal infections like salmonellosis could contribute to CC development. We performed a nationwide registry study to assess potential associations between occupation (history) and CC, including also those occupations with known increased exposure to gastrointestinal pathogens like Salmonella. Methods Person-level occupational data for all residents in The Netherlands were linked to CC diagnosis data. Differences in the incidence of (overall, proximal and distal) CC among occupational sectors and risk groups were tested for significance by calculating standardised incidence ratios (SIRs) with 95% CIs using the general population as reference group. Effects of gender, age, exposure duration and latency were also assessed. Results Significant differences in CC incidence were observed only for a few occupational sectors, including the manufacturing of rubber and plastics, machinery and leather, the printing sector and the information service sector (SIRs 1.06-1.88). No elevated risk of CC was observed among people with increased salmonellosis risk through occupational exposure to live animals, manure or among those working in the sale of animal-derived food products (SIRs 0.93-0.95, 0.81-0.95 and 0.93-1.09 for overall, proximal and distal CC, respectively). Conclusions The results of this study suggest that occupation in itself provides a relatively small contribution to CC incidence. This is consistent with previous studies where a similar degree of variation in risk estimates was observed. The lack of an association with the high-risk occupations for salmonellosis might be due to higher levels of physical activity, a known protective factor for CC and other diseases, of people working in the agricultural sector, which might outweigh the potential Salmonella-associated risk of CC. Show less
Lohman, E.D.; Duijster, J.; Koerkamp, B.G.; Post, R. van der; Franz, E.; Gras, L.M.; Reuver, P. de 2020
