International travel and acquisition of multidrug-resistant Enterobacteriaceae: a systematic review

International travel is considered to be an important risk factor for acquisition of multidrug-resistant Enterobacteriaceae (MRE). The aim of this systematic review was to determine the effect of international travel on the risk of post-travel faecal carriage of MRE. Secondary outcomes were risk factors for acquisition of MRE. A systematic search for relevant literature in seven international databases was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles needed to report on (i) foreign travel, (ii) screening of asymptomatic participants, (iii) antimicrobial susceptibility data and (iv) faecal Enterobacteriaceae carriage. Two researchers independently screened the abstracts, assessed the full article texts for eligibility and selected or rejected them for inclusion in the systematic review. In case of disagreement, a third researcher decided on inclusion. Eleven studies were identified. In all studies, a high prevalence (> 20%) of carriage of MRE after international travel was found. The highest prevalence was observed in travellers returning from southern Asia. Foreign travel was associated with an increased risk of carriage of MRE. Further research is needed to assess if this leads to an increase in the number of infections with MRE. Systematic review registration number: PROSPERO CRD42015024973

Severe leptospirosis in a Dutch traveller returning from the Dominican Republic, October 2011

In October 2011, a case of leptospirosis was identified in a Dutch traveller returning from the Dominican Republic to the Netherlands. The 51-year-old man had aspired muddy water in the Chavón river on 29 September. Twenty days later he presented with fever, nausea, vomiting, diarrhoea, arthralgia, headache, conjunctival suffusion and icterus. Leptospira serovar Icterohaemorrhagiae or Australis infection was confirmed ten days later by laboratory testing

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

The Carriage of Multiresistant Bacteria after Travel (COMBAT) prospective cohort study: Methodology and design

Background: Antimicrobial resistance (AMR) is one of the major threats to public health around the world. Besides the intense use and misuse of antimicrobial agents as the major force behind the increase in antimicrobial resistance, the e

Import and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study

BACKGROUND: International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation, and probability of onward transmission. METHODS: Within the prospective, multicentre COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behaviour were collected before travel and immediately and 1, 3, 6, and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded β-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 was used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. This study is registered with ClinicalTrials.gov, number NCT01676974. FINDINGS: 633 (34·3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32·1-36·5), with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75·1%, 95% CI 68·4-80·9). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2·69, 95% CI 1·79-4·05), traveller's diarrhoea that persisted after return (2·31, 1·42-3·76), and pre-existing chronic bowel disease (2·10, 1·13-3·90). The median duration of colonisation after travel was 30 days (95% CI 29-33). 65 (11·3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days, 95% CI 48-102, p=0·0001). Onward transmission was found in 13 (7·7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5-18). INTERPRETATION: Acquisition and spread of ESBL-E during and after international travel was substantial and worrisome. Travellers to areas with a high risk of ESBL-E acquisition should be viewed as potential carriers of ESBL-E for up to 12 months after return. FUNDING: Netherlands Organisation for Health Research and Development (ZonMw)

Prevalence and risk factors for carriage of ESBL-producing Enterobacteriaceae in a population of Dutch travellers: A cross-sectional study

Background: We investigated prevalence and predictive factors for ESBL-E carriage in a population of mostly travellers prior to their travel (n = 2216). In addition, we examined ESBL genotype before travel and compared these to returning travellers. Method: A questionnaire and faecal sample were collected before travel, and a second faecal sample was collected immediately after travel. Faecal samples were analysed for ESBL-E, with genotypic characterization by PCR and sequencing. Risk factors for ESBL-E carriage prior to travel were identified by logistic regression analyses. Results: Before travel, 136 participants (6.1%) were colonized with ESBL-E. Antibiotic use in the past three months (ORadjusted 2.57; 95% CI 1.59–4.16) and travel outside of Europe in the past year (1.92, 1.28–2.87) were risk factors for ESBL-E colonisation prior to travel. Travel outside of Europe carried the largest attributable risk (39.8%). Prior to travel 31.3% (40/128) of participants carried blaCTX-M 15 and 21.9% (28/128) blaCTX-M 14/18. In returning travellers 633 acquired ESBL-E of who 53.4% (338/633) acquired blaCTX-M 15 and 17.7% (112/633) blaCTX-M 14/18. Conclusion: In our population of Dutch travellers we found a pre-travel ESBL-E prevalence of 6.1%. Prior to travel, previous antibiotic use and travel outside of Europe were the strongest independent predictors

Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction

To understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the IncI2, IncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of IncHI2 plasmids in Europe and IncI2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types

Carriage of Blastocystis spp. in travellers - A prospective longitudinal study

Introduction: A lack of prospective and longitudinal data on pre- and post-travel carriage of Blastocystis spp. complicates interpretation of a positive test post-travel. Therefore we studied dynamics of Blastocystis carriage in a cohort of Dutch travellers. Methods: From the prospective, multicentre COMBAT study among 2001 Dutch travellers, a subset of 491 travellers was selected based on travel destination to 7 subregions (70 or 71 travellers each). Faecal samples taken directly before and after travel were screened for Blastocystis with qPCR, followed, when positive, by sequence analysis to determine subtypes. Results: After exclusion of 12 samples with missing samples or inhibited qPCR-reactions, stool samples of 479 travellers were analysed. Before travel, 174 of them (36.3%) carried Blastocystis and in most of these, the same subtype was persistently carried. However, in 48/174 of those travellers (27.6%; CI95 20.8–36.6%) no Blastocystis or a different subtype was detected in the post-travel sample, indicating loss of Blastocystis during travel. Only 26 (5.4%; CI95 3.7%–8.0%) of all travellers acquired Blastocystis, including two individuals that were already positive for Blastocystis before travel but acquired a different subtype during travel. Discussion: This study shows that Blastocystis carriage in travellers is highly dynamic. The observed acquisition and loss of Blastocystis could either be travel-related or reflect the natural course of Blastocystis carriage. We demonstrate that the majority of Blastocystis detected in post-travel samples were already carried before travel

The Import and Spread of Antibiotic-Resistant Enterobacteriaceae by Healthy Travellers

Background International travel contributes to the dissemination of antimicrobial resistance. We examined the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation and probability of onward transmission. The presented data were published before in The Lancet Infectious Diseases. Methods Within the prospective multicenter COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behavior were collected before and immediately after travel, and at 1, 3, 6 and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded beta-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 were used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. Finding

Conservation from the bottom up: drawing inspiration from human-nature connections

Increasing exploitation and commodification of the world’s species and natural systems threaten biological diversity as well as human cultural diversity. Approximately 1000 known species and an estimated half of the world’s languages have gone extinct over the last 500 years. Increasing human populations and impacts may threaten 30-50% of remaining species within the next several decades, and many extant languages are in danger of extinction, illustrating how the fates of both biological and human cultural diversity may be entwined. We explore challenges and opportunities to stem this tide of homogenization using cultural traditions that have conservation implications. We highlight case studies with birds in Europe, Africa, Amazonia, and Asia, including examples from Latvia, Ghana, Peru, and Taiwan. We present examples of successful conservation collaborations inspired by cultural beliefs and practices, and ask workshop participants to come with their own stories to share. One example is indigenous Amazonian communities who are working with scientists to protect and sustainably manage a large area of primary forest and its birds in northern Peru, and whose cultural heritage includes a large number of traditional stories of birds as messengers to and helpers of people. How can we take inspiration from cultural traditions celebrating biodiversity and use these for conservation innovation, propelling the conservation movement forward and protecting unique species, areas, and cultures into the future? Our goal is to bring together and build a network of people advancing conservation through innovative initiatives that incorporate or transform cultural traditions and practices. We will use group discussion and brainstorming to create new collaborations, bringing together salient experiences we can use to advance conservation. We will document the experiences shared during the workshop and use these to make the basis of an article on conservation innovation that we will offer for consideration in the special issue on planetary wellbeing in Conservation Biology. This article will include case studies from around the world (Europe, Africa, Asia-Pacific, the Americas) that use cultural traditions as a basis for conservation, both historically, currently, and those proposed for the future.peerReviewe