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Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014-2019: a cross-sectional analytical study.

ABSTRACT: Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics.Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns.Aim. By characterising factors associated with antimicrobial resistance in cases of S. Typhi and S. Paratyphi imported to England, we aim to guide effective empirical treatment.Methodology. All English isolates of S. Typhi and S. Paratyphi 2014-2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005-2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance.Results. We identified 1088 cases of S. Typhi, 729 S. Paratyphi A, 93 S. Paratyphi B, and one S. Paratyphi C. In total, 93 % were imported. Overall, 90 % of S. Typhi and 97 % of S. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S. Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S. Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4-66.4), India (aOR=21.8, 95 % CI: 11.6-41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8-13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S. Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4-5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04-0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005-2012 London survey indicates substantial increases in the prevalence of resistance of S. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79-98 %) and Africa (from 12-60 %).Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.

SUBMITTER: Herdman MT

PROVIDER: S-EPMC8513630 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Malaria remains the most common specific cause of fever in returned travellers and can be life-threatening. We examined demographic and travel correlates of malaria among Canadian travellers and immigrants to identify groups for targeted pretravel intervention.Descriptive data on ill returned Canadian travellers and immigrants presenting to a CanTravNet site between 2004 and 2014 with a diagnosis of malaria were analyzed. Data were collected using the GeoSentinel data platform. This network comprises 63 specialized travel and tropical medicine clinics, including 7 Canadian sites (Vancouver, Calgary, Toronto, Ottawa, Winnipeg and Montréal), that contribute anonymous, delinked, clinician- and questionnaire-based travel surveillance data on all ill travellers examined to a centralized Structure Query Language database.During the study period, 20?345 travellers and immigrants were evaluated, and 93% had a travel-related diagnosis. Of these, 437 (2.1%) patients received 456 malaria diagnoses, the most common species being Plasmodium falciparum (n = 282, 61.8%). People travelling to visit friends and relatives were most well-represented (n = 169, 38.7%), followed by business travellers (n = 71, 16.2%). Sub-Saharan Africa was the most common source region, accounting for 341 (74.8%) malaria diagnoses, followed by South Central Asia (n = 55, 12%). Nigeria was the most well-represented source country, accounting for 41 cases (9.0%). India, a high-volume destination for Canadians, accounted for 40 cases (8.8%), 36 of which were caused by Plasmodium vivax. Of 456 malaria diagnoses, 26 (5.7%) were severe. Of 377 nonimmigrant travellers with malaria, 19.9% (n = 75) travelled for less than 2 weeks, and 7.2% (n = 27) travelled for less than 1 week.This analysis provides an epidemiologic framework for Canadian practitioners encountering prospective and returned travellers. It confirms the importance of preventive measures and surveillance associated with travel to sub-Saharan Africa and India, particularly by travellers visiting friends or relatives. Short-duration travel confers important malaria risk.

Project description:BackgroundClinical observations suggest that Canadian-born (CB) travellers are prone to more severe malaria, characterized by higher parasite density in the blood, and severe symptoms, such as cerebral malaria and renal failure, than foreign-born travellers (FB) from areas of malaria endemicity. It was hypothesized that host cytokine and chemokine responses differ significantly in CB versus FB patients returning with malaria, contributing to the courses of severity. A more detailed understanding of the profiles of cytokines, chemokines, and endothelial activation may be useful in developing biomarkers and novel therapeutic approaches for malaria.Materials and methodsThe patient population for the study (n = 186) was comprised of travellers returning to Toronto, Canada between 2007 and 2011. The patient blood samples' cytokine, chemokine and angiopoietin concentrations were determined using cytokine multiplex assays, and ELISA assays.ResultsSignificantly higher plasma cytokine levels of IL-12 (p40) were observed in CB compared to FB travellers, while epidermal growth factor (EGF) was observed to be higher in FB than CB travellers. Older travellers (55 years old or greater) with Plasmodium vivax infections had significantly higher mean cytokine levels for IL-6 and macrophage colony-stimulating factor (M-CSF) than other adults with P. vivax (ages 18-55). Patients with P. vivax infections had significantly higher mean cytokine levels for monocyte chemotactic protein-1 (MCP-1), and M-CSF than patients with Plasmodium falciparum. Angiopoietin 2 (Ang-2) was higher for patients infected with P. falciparum than P. vivax, especially when comparing just the FB groups. IL-12 (p40) was higher in FB patients with P. vivax compared to P. falciparum. Il-12 (p40) was also higher in patients infected with P. vivax than those infected with Plasmodium ovale. For patients travelling to West Africa, IFN-γ and IL-6 was lower than for patients who were in other regions of Africa.ConclusionSignificantly higher levels of IL-12 (p40) and lower levels of EGF in CB travellers may serve as useful prognostic markers of disease severity and help guide clinical management upon return. IL-6 and M-CSF in older adults and MCP-1, IL-12 (p40) and M-CSF for P. vivax infected patients may also prove useful in understanding age-associated and species-specific host immune responses, as could the species-specific differences in Ang-2. Regional differences in host immune response to malaria infection within the same species may speak to unique strains circulating in parts of West Africa.

Project description:BackgroundLeishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines.Methodology/principal findingsEnglish literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice.Conclusions/significanceOur study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.

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Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014-2019: a cross-sectional analytical study.

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