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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 exponential increase of international travel may also substantially contribute to the emergence and spread of AMR. However, knowledge on the extent to which international travel contributes to this is still limited. The Carriage Of Multiresistant Bacteria After Travel (COMBAT) study aims to 1. determine the acquisition rate of multiresistant Enterobacteriaceae during foreign travel 2. ascertain the duration of carriage of these micro-organisms 3. determine the transmission rate within households 4. identify risk factors for acquisition, persistence of carriage and transmission of multiresistant Enterobacteriaceae. METHODS/DESIGN: The COMBAT-study is a large-scale multicenter longitudinal cohort study among travellers (n = 2001) and their non-travelling household members (n = 215). Faecal samples are collected before and immediately after travel and 1 month after return from all participants. Follow-up faecal samples are collected 3, 6 and 12 months after return from travellers (and their non-travelling household members) who acquired multiresistant Enterobacteriaceae. Questionnaires are collected from all participants at each time-point. Faecal samples are screened phenotypically for the presence of extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing Enterobacteriaceae. Positive post-travel isolates from travellers with negative pre-travel samples are genotypically analysed for ESBL and carbapenemase genes with microarray and gene sequencing. DISCUSSION: The design and scale of the COMBAT-study will enable us to provide much needed detailed insights into the risks and dynamics of introduction and spread of ESBL- and carbapenemase-producing Enterobacteriaceae by healthy travellers and the potential need and measures to monitor or manage these risks. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov under accession number NCT01676974.
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Infecções por Enterobacteriaceae/epidemiologia , Viagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/metabolismo , Estudos de Coortes , Farmacorresistência Bacteriana , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/prevenção & controle , Fezes/microbiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , beta-Lactamases/metabolismoRESUMO
Objectives: Extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec) are frequently acquired during international travel, contributing to the global spread of antimicrobial resistance. Human-adapted ESBL-Ec are predicted to exhibit increased intestinal carriage duration, resulting in a higher likelihood of onward human-to-human transmission. Yet, bacterial determinants of increased carriage duration are unknown. Previous studies analysed small traveller cohorts, with short follow-up times, or did not employ high-resolution molecular typing, and were thus unable to identify bacterial traits associated with long-term carriage after recent acquisition. We aimed to identify which ESBL-Ec lineages are associated with increased carriage duration after return from international travel. Methods: In a prospective cohort study of 2001 international travellers, we analysed 160 faecal ESBL-Ec isolates from all 38 travellers who acquired ESBL-Ec during travel and subsequently carried ESBL-Ec for at least 12 months after return, by whole-genome sequencing. For 17 travellers, we confirmed the long-term carriage of ESBL-Ec strains through single nucleotide variant typing. To identify determinants of increased carriage duration, we compared the 17 long-term carriers (≥12 months of carriage) with 33 age-, sex- and destination-matched short-term carriers (<1 month of carriage). Long-read sequencing was employed to investigate long-term ESBL plasmid carriage. Results: We show that in healthy travellers with very low antibiotic usage, extra-intestinal pathogenic lineages of E. coli (ExPEC) are significantly more likely to persist than other E. coli lineages. The long-term carriage of E. coli from ExPEC lineages is mainly driven by sequence type 131 and phylogroup D E. coli. Conclusions: Although ExPEC lineages frequently cause extra-intestinal infections such as bloodstream infections, our results indicate that ExPEC lineages are also efficient intestinal colonizers, which potentially contributes to their onward transmission.
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PURPOSE: Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients. METHODS: Mechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients. RESULTS: Pulmonary reactivation (> 104 copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04-1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1ß, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF). CONCLUSION: In mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation.
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COVID-19 , Infecções por Citomegalovirus , Citomegalovirus , Síndrome do Desconforto Respiratório , Carga Viral , Humanos , COVID-19/complicações , COVID-19/fisiopatologia , COVID-19/mortalidade , COVID-19/epidemiologia , Masculino , Síndrome do Desconforto Respiratório/virologia , Pessoa de Meia-Idade , Feminino , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Idoso , Citomegalovirus/isolamento & purificação , Citomegalovirus/patogenicidade , Simplexvirus/patogenicidade , Simplexvirus/isolamento & purificação , Ativação Viral , Respiração Artificial/estatística & dados numéricos , Herpes Simples/complicações , Herpes Simples/epidemiologia , Herpes Simples/diagnóstico , SARS-CoV-2 , Antivirais/uso terapêutico , Estudos de CoortesRESUMO
We studied clinical characteristics, appropriateness of initial antibiotic treatment, and other factors associated with day 30 mortality in patients with bacteremia caused by extended-spectrum-ß-lactamase (ESBL)-producing bacteria in eight Dutch hospitals. Retrospectively, information was collected from 232 consecutive patients with ESBL bacteremia (due to Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae) between 2008 and 2010. In this cohort (median age of 65 years; 24 patients were <18 years of age), many had comorbidities, such as malignancy (34%) or recurrent urinary tract infection (UTI) (15%). One hundred forty episodes (60%) were nosocomial, 54 (23%) were otherwise health care associated, and 38 (16%) were community acquired. The most frequent sources of infection were UTI (42%) and intra-abdominal infection (28%). Appropriate therapy within 24 h after bacteremia onset was prescribed to 37% of all patients and to 54% of known ESBL carriers. The day 30 mortality rate was 20%. In a multivariable analysis, a Charlson comorbidity index of ≥ 3, an age of ≥ 75 years, intensive care unit (ICU) stay at bacteremia onset, a non-UTI bacteremia source, and presentation with severe sepsis, but not inappropriate therapy within <24 h (adjusted odds ratio [OR], 1.53; 95% confidence interval [CI], 0.68 to 3.45), were associated with day 30 mortality. Further assessment of confounding and a stratified analysis for patients with UTI and non-UTI origins of infection did not reveal a statistically significant effect of inappropriate therapy on day 30 mortality, and these results were insensitive to the possible misclassification of patients who had received ß-lactam-ß-lactamase inhibitor combinations or ceftazidime as initial treatment. In conclusion, ESBL bacteremia occurs mostly in patients with comorbidities requiring frequent hospitalization, and 84% of episodes were health care associated. Factors other than inappropriate therapy within <24 h determined day 30 mortality.
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Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , beta-Lactamas/uso terapêutico , Idoso , Bacteriemia/microbiologia , Comorbidade , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Enterobacter cloacae/efeitos dos fármacos , Infecções por Enterobacteriaceae/mortalidade , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Feminino , Humanos , Infecções Intra-Abdominais , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Resultado do Tratamento , Resistência beta-Lactâmica/genética , beta-Lactamases/biossíntese , beta-Lactamas/farmacologiaRESUMO
Drug reactions are common and have a major impact on prescribing behaviour in the Netherlands. An adequate allergy registration is essential both to avoid re-exposition and to prevent unnecessary avoidance. An incomplete or incorrect registration of allergies is a threat to good medical practice, unnecessarily leading to sub-optimal treatment. National registries such as the Dutch 'LandelijkSchakelpunt' (LSP), must be easily accessible to all care providers and kept up-to-date. Healthcare providers should be properly trained in recognizing allergies as well as correct allergy registration. Additionally, healthcare providers must be given the opportunity to register as well as delete allergies from registry systems.
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Hipersensibilidade a Drogas , Humanos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/prevenção & controle , Sistema de Registros , Países BaixosRESUMO
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.
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Infecções por Enterobacteriaceae , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Bacteroidaceae , Diarreia/tratamento farmacológico , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/genética , Humanos , Viagem , beta-Lactamases/genética , beta-Lactamases/farmacologiaRESUMO
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's 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' 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, blaCTX-M family extended-spectrum ß-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. 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.
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Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Resistência Microbiana a Medicamentos , Doença Relacionada a Viagens , Biologia Computacional/métodos , Bases de Dados Genéticas , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metagenoma , Metagenômica , Países Baixos/epidemiologia , Vigilância em Saúde Pública , beta-Lactamases/genéticaRESUMO
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 for ESBL-E carriage, with travel outside of Europe carrying the largest attributable risk. Our molecular results suggest ESBL genes found in our study population prior to travel were in large part travel related.
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Portador Sadio/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Doença Relacionada a Viagens , Antibacterianos/uso terapêutico , Estudos Transversais , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/genética , Fezes/microbiologia , Genótipo , Humanos , Países Baixos/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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16S rRNA gene sequencing is a useful tool for identification of non-cultured or hard-to-identify bacteria. This technique can be used to detect and identify bacteria in clinical materials, such as cerebrospinal fluid and heart valves, if conventional methods do not reveal pathogens. A major advantage compared with other techniques is that it is not necessary to know in advance what pathogen is the likely cause of the disease. An important drawback is the background noise generated by traces of bacterial DNA in reagents.
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Bactérias/genética , DNA Bacteriano , RNA Ribossômico 16S , Humanos , Análise de Sequência de DNA/métodosRESUMO
OBJECTIVES: The incidence of neonatal herpes simplex virus (nHSV) infections is monitored periodically in the Netherlands, yet management and outcome is unknown. Comprehensive national guidelines are lacking. We aim to describe management and outcome in the last decade to explore current diagnostic and therapeutic challenges. We aim to identify possible variability in management of patients with a suspected nHSV infection. METHODS: We conducted a retrospective case series of management and outcome of nHSV infections at 2 tertiary care center locations in the Netherlands. RESULTS: An nHSV infection was diagnosed in 1% (12 of 1348) of patients in whom polymerase chain reaction for HSV was performed. Of the patients with nHSV infection, 3 of 12 died, and 4 of 9 (44%) survivors suffered neurologic sequelae. Neurologic symptoms at presentation were seen in only 2 of 8 patients with nHSV encephalitis. A cerebral spinal fluid analysis was performed in 3 of 6 patients presenting with skin lesions. Only 3 of 6 patients with neurologic symptoms received suppressive therapy. nHSV infection was diagnosed in 8 of 189 (4%) patients who were empirically treated. CONCLUSIONS: Management of nHSV infection, particularly when presented with skin lesions, is inconsistent. Many infants without a HSV infection are exposed to antiviral medication. There is substantial interhospital variation in diagnostic and therapeutic management of a suspected infection. Comprehensive guidelines need to be developed to standardize management of suspected nHSV infection.
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Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Encefalite por Herpes Simples/terapia , Herpes Simples/terapia , Padrões de Prática Médica , Gerenciamento Clínico , Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/mortalidade , Feminino , Herpes Simples/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Países Baixos , Reação em Cadeia da PolimeraseRESUMO
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.
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Antimaláricos/uso terapêutico , Malária/etnologia , Complicações Parasitárias na Gravidez/epidemiologia , Viagem , Feminino , Humanos , Malária/tratamento farmacológico , Vacinas Antimaláricas , Países Baixos/epidemiologia , Gravidez , Complicações Parasitárias na Gravidez/tratamento farmacológicoRESUMO
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.
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Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Viagem , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina , Cloroquina/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Malária/diagnóstico , Vacinas Antimaláricas/uso terapêutico , Masculino , Países Baixos , GravidezRESUMO
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.
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Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Escherichia coli/patogenicidade , Viagem , Fatores de Virulência/genética , Fezes/microbiologia , Transferência Genética Horizontal , Humanos , Países Baixos , Estudos Prospectivos , RiscoRESUMO
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.
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Infecções por Blastocystis/epidemiologia , Portador Sadio/parasitologia , Fezes/parasitologia , Viagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Blastocystis/genética , Portador Sadio/epidemiologia , Feminino , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Adulto JovemRESUMO
OVERVIEW: 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. THE CASE: 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. DISCUSSION: 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.
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Cancroide/microbiologia , Haemophilus ducreyi/isolamento & purificação , Úlcera Cutânea/microbiologia , Viagem , Cancroide/tratamento farmacológico , Ciprofloxacina/uso terapêutico , Humanos , Indonésia , Masculino , Países Baixos , Úlcera Cutânea/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum ß-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 ß-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).
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Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/enzimologia , Viagem , beta-Lactamases , Antibacterianos/uso terapêutico , Diarreia/etiologia , Infecções por Enterobacteriaceae/transmissão , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de TempoRESUMO
BACKGROUND: Limited prospective data are available on the acquisition of viral, bacterial and parasitic diarrhoeagenic agents by healthy individuals during travel. METHODS: To determine the frequency of travel associated acquisition of 19 pathogens in 98 intercontinental travellers, qPCR was used to detect 8 viral pathogens, 6 bacterial enteric pathogens and 5 parasite species in faecal samples collected immediately before and after travel. RESULTS: We found high pre-travel carriage rates of Blastocystis spp. and Dientamoeba fragilis of 32% and 19% respectively. Pre-travel prevalences of all other tested pathogens were below 3%. Blastocystis spp. (10%), Plesiomonas shigelloides (7%), D. fragilis (6%) and Shigella spp. (5%) were the most frequently acquired pathogens and acquisition of enteral viruses and hepatitis E virus in this relatively small group of travellers was rare or non-existent. CONCLUSIONS: Our findings suggest that the role of viruses as the cause of persisting traveller's diarrhoea is limited and bacterial pathogens are more likely as a cause of traveller's diarrhoea. The substantial proportion of travellers carrying Blastocystis spp. and D. fragilis before travel warrants cautious interpretation of positive samples in returning travellers with gastrointestinal complaints.