Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

BACKGROUND: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel\u27s effects on the gut resistome remain largely unknown. METHODS: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. RESULTS: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers\u27 gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, bla CONCLUSIONS: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Risk of acquisition of human diarrhoeagenic Escherichia coli virulence genes in intercontinental travellers: A prospective, multi-centre study

COMBAT consortium: et al.[Background]: We studied geographic distribution of diarrhoeagenic Escherichia coli virulence genes (DEC VGs) acquisition in travellers and investigated if they acquired highly virulent EAEC/STEC hybrid strains.[Methods]: From the prospective, multicentre COMBAT study among 2001 Dutch travellers, 491 travellers were selected based on travel destination to 7 subregions. Faecal samples taken directly before and after travel were screened for nine DEC VGs with real-time PCR. Incidence proportions and rates were calculated for each gene and subregion.[Results]: 479 travellers were analysed. 21.8% acquired aggR (EAEC), with highest acquisition rates in Northern and Western Africa and 15.3% acquired eae (STEC/EPEC) with highest rates in travellers to Western and Eastern Africa. ETEC (elt or est gene) was acquired by 4.2% of travellers and acquisition of est was associated with traveller's diarrhoea. Overall, the risk of acquiring DEC VGs was low in Southern Africa and South America. Although the combination of aggR (EAEC) and stx1/2 (STEC) was acquired by 3 travellers, these genes could not be detected together in a single E. coli strain.[Conclusions]: The risk of acquisition of DEC VGs strongly depends on the travel destination, with those travelling to Africa - except Southern Africa - having a higher risk.The COMBAT-study was funded by Netherlands Organisation for Health Research and Development (ZonMw, grant number 205200003). This work is a contribution to EU FP7 ANTIGONE (project number 278976).Peer reviewe

Topical silver for treating infected wounds

Background: Topical silver treatments and silver dressings are increasingly used for the local treatment of contaminated or infected wounds, however, there is a lack of clarity regarding the evidence for their effectiveness. Objectives: To evaluate the effects on wound healing of topical silver and silver dressings in the treatment of contaminated and infected acute or chronic wounds. Search strategy: We sought relevant trials from the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Wounds Group Specialised Register in March 2006 and in MEDLINE, EMBASE, CINAHL, and digital dissertations databases up to September 2006. In addition, we contacted companies, manufacturers and distributors for information to identify relevant trials. Selection criteria: Randomised controlled trials (RCTs) assessing the effectiveness of topical silver in the treatment of contaminated and infected acute or chronic wounds. Data collection and analysis: Eligibility of trials, assessment of trial quality and data extraction were undertaken by two authors independently. Disagreements were referred to a third author. Main results: Three RCTs were identified, comprising a total of 847 participants. One trial compared silver-containing foam (Contreet®) with hydrocellular foam (Allevyn®) in patients with leg ulcers. The second trial compared a silver-containing alginate (Silvercel®) with an alginate alone (Algosteril®). The third trial compared a silver-containing foam dressing (Contreet®)) with best local practice in patients with chronic wounds. The data from these trials show that silver-containing foam dressings did not significantly increase complete ulcer healing as compared with standard foam dressings or best local practice after up to four weeks of follow-up, although a greater reduction of ulcer size was observed with the silver-containing foam. The use of antibiotics was assessed in two trials, but no significant differences were found. Data on pain, patient satisfaction, length of hospital stay, and costs were limited and showed no differences. Leakage occurred significantly less frequently in patients with leg ulcers and chronic wounds treated with a silver dressing than with a standard foam dressing or best local practice in one trial. Authors' conclusions: Only three trials with a short follow-up duration were found. There is insufficient evidence to recommend the use of silver-containing dressings or topical agents for treatment of infected or contaminated chronic wounds

De behandeling van malaria

In the Netherlands, approximately 200 to 300 patients are diagnosed with imported malaria every year. The symptoms of malaria are non-specific. The current gold standard for malaria diagnostics is to conduct a thick and thin blood smear. New diagnostic techniques are increasingly applied. At present, the treatment of uncomplicated malaria consists of an artemisinin-based combination therapy (ACT). An alternative treatment for malaria caused by P. vivax,P. knowlesi,P. ovale and P. malariae in the Netherlands is chloroquine. Severe malaria is treated with artesunate intravenously, followed by a full three-day course of oral ACT. Uncomplicated malaria during pregnancy is treated with an ACT (e.g. artemether-lumefantrine) and severe malaria with artesunate intravenously, the latter followed by a full three-day course of oral ACT. There is currently no malaria vaccine available for travellers

Haemophilus ducreyi cutaneous ulcer contracted at Seram Island, Indonesia, presented in the Netherlands.

We describe the first case of a cutaneous ulcer caused by Haemophilus ducreyi imported from Indonesia to the Netherlands. Skin infections caused by H. ducreyi are uncommon in travellers and have been described in just a few case reports and were all contracted on the Pacific Islands.A 22-year-old healthy male visited the Center of Tropical Medicine and Travel Medicine in February 2017 with a cutaneous ulcer of the right lateral malleolus 4 weeks after returning from Indonesia (Seram and Ambon Islands). He had noticed a small skin abrasion on the right ankle after slipping on a rock during a jungle trip on Seram Island. Back in the Netherlands, a painful ulcer developed at the same body location, and despite treatment with flucloxacillin, his complaints worsened. A swab that was taken for culture showed growth of small grey colonies that were characterised as H. ducreyi with matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry. Treatment with ciprofloxacin for the diagnosis of H. ducreyi cutaneous ulcer was started, and the ulcer clearly diminished, leaving only a small healing ulcer.H. ducreyi is normally the causative agent of genital ulcers but is increasingly recognised as a cause of chronic skin ulcers, e.g., in Papua New Guinea. In our patient, the infection was very likely contracted in the Maluku province of Indonesia and imported into the Netherlands. No reports of infection with H. ducreyi from Indonesia could be found in literature, but this case indicates that H. ducreyi is present in at least one of the northeastern islands of Indonesia, which is important for local healthcare. Additionally, it illustrates the role of this agent as a cause of cutaneous ulcers in previously healthy travellers

Enterobacteriaceae and Bacteroidaceae provide resistance to travel-associated intestinal colonization by multi-drug resistant Escherichia coli

Previous studies have shown high acquisition risks of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) among international travelers visiting antimicrobial resistance (AMR) hotspots. Although antibiotic use and travelers' diarrhea have shown to influence the ESBL-E acquisition risk, it remains largely unknown whether successful colonization of ESBL-E during travel is associated with the composition, functional capacity and resilience of the traveler's microbiome. The microbiome of pre- and post-travel fecal samples from 190 international travelers visiting Africa or Asia was profiled using whole metagenome shotgun sequencing. A metagenomics species concept approach was used to determine the microbial composition, population diversity and functional capacity before travel and how it is altered longitudinally. Eleven travelers were positive for ESBL-E before travel and removed from the analysis. Neither the microbial richness (Chao1), diversity (effective Shannon) and community structure (Bray-Curtis dissimilarity) in pretravel samples nor the longitudinal change of these metrics during travel were predictive for ESBL-E acquisition. A zero-inflated two-step beta-regression model was used to determine how the longitudinal change in both prevalence and abundance of each taxon was related to ESBL acquisition. There were detected increases in both the prevalence and abundance of Citrobacter freundii and two members of the genus Bacteroides, in association with remaining uncolonized by ESBL-E. These results highlight the potential of these individual microbes as a microbial consortium to prevent the acquisition of ESBL-E. The ability to alter a person's colonization resistance to a bacterium could be key to intervention strategies that aim to minimize the spread of MDR bacteria

Enterobacteriaceae and Bacteroidaceae provide resistance to travel-associated intestinal colonization by multi-drug resistant Escherichia coli

Previous studies have shown high acquisition risks of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) among international travelers visiting antimicrobial resistance (AMR) hotspots. Although antibiotic use and travelers' diarrhea have shown to influence the ESBL-E acquisition risk, it remains largely unknown whether successful colonization of ESBL-E during travel is associated with the composition, functional capacity and resilience of the traveler's microbiome. The microbiome of pre- and post-travel fecal samples from 190 international travelers visiting Africa or Asia was profiled using whole metagenome shotgun sequencing. A metagenomics species concept approach was used to determine the microbial composition, population diversity and functional capacity before travel and how it is altered longitudinally. Eleven travelers were positive for ESBL-E before travel and removed from the analysis. Neither the microbial richness (Chao1), diversity (effective Shannon) and community structure (Bray-Curtis dissimilarity) in pretravel samples nor the longitudinal change of these metrics during travel were predictive for ESBL-E acquisition. A zero-inflated two-step beta-regression model was used to determine how the longitudinal change in both prevalence and abundance of each taxon was related to ESBL acquisition. There were detected increases in both the prevalence and abundance of Citrobacter freundii and two members of the genus Bacteroides, in association with remaining uncolonized by ESBL-E. These results highlight the potential of these individual microbes as a microbial consortium to prevent the acquisition of ESBL-E. The ability to alter a person's colonization resistance to a bacterium could be key to intervention strategies that aim to minimize the spread of MDR bacteria