Epidemiology of non-travel enteric fever cases in England: insights from 10 years of surveillance.

OBJECTIVES: In non-endemic countries, surveillance of non-travel cases of enteric fever is important to identify carriers and reduce secondary transmission. We characterised these cases in England between 2012 and 2021 and assessed potential sources of infection to inform guidance revision. STUDY DESIGN: Retrospective case-case. METHODS: We identified enteric fever cases from the national surveillance dataset. Non-travel cases were defined as no travel to an endemic country or travel but onset of >60 days after return. Multivariable logistic regression was used to identify factors associated with non-travel cases. We reviewed the case records of cases with unknown source of infection. RESULTS: Compared to travel cases, non-travel cases (7%; 225/3075) were older (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.02-1.04), asymptomatic (OR = 9.3: 95% CI: 4.3-20.3), and confirmed with Salmonella typhi infection (OR = 1.74, 95% CI: 1.26-2.4). Non-travel cases had lower odds of being of Indian (OR = 0.27, 95% CI: 0.16-0.45) or Pakistani ethnicity (OR = 0.34, 95% CI: 0.16-0.45) than White British. Surveillance questionnaires identified a possible infection source for 53%: case records review identified a further 23%: 33% secondary transmission, mostly household; 21% had overseas visitors, or travelling family; 12% were carriers (cases with enteric fever in the past), 12% travelled to endemic country outside of the 60-day window, and 22% had other possible sources. Case records differentiated between travel 60-90 days (5%) vs travel years prior to onset (7%), suggesting carrier status. CONCLUSION: Not all possible carriers were identified through the surveillance questionnaire. Therefore, we recommend additional questions to systematically capture travel history beyond 60 days to assist in classifying carrier status and to updating the source of infection.

Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action.

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

Socioeconomic and ethnic inequalities in incidence and severity of enteric fever in England 2015-2019: analysis of a national enhanced surveillance system.

There is limited research on whether inequalities exist among individuals from different ethnicities and deprivation status among enteric fever cases. The aim of the study was to investigate the association between the enteric fever incidence rates, ethnicity and deprivation for enteric fever cases in England. Additionally, it was assessed if ethnicity and deprivation were associated with symptom severity, hospital admission and absence from school/work using logistic regression models. Incidence rates were higher in the two most deprived index of multiple deprivation quintiles and those of Pakistani ethnicity (9.89, 95% CI 9.08-10.75) followed by Indian (7.81, 95% CI 7.18-8.49) and Bangladeshi (5.68, 95% CI 4.74-6.76) groups: the incidence rate in the White group was 0.07 (95% CI 0.06-0.08). Individuals representing Pakistani (3.00, 95% CI 1.66-5.43), Indian (2.05, 95% CI 1.18-3.54) and Other/Other Asian (3.51, 95% CI 1.52-8.14) ethnicities had significantly higher odds of hospital admission than individuals representing White (British/Other) ethnicity, although all three groups had statistically significantly lower symptom severity scores. Our results show that there are significant ethnic and socioeconomic inequalities in enteric fever incidence that should inform prevention and treatment strategies. Targeted, community-specific public health interventions are needed to impact on overall burden.

Genomic sentinel surveillance: Salmonella Paratyphi B outbreak in travellers coinciding with a mass gathering in Iraq.

Salmonella Paratyphi B infections in England are the least common imported typhoidal infection but can still cause invasive disease. Sentinel surveillance at the reference laboratory detected an outbreak from Iraq due to reported travel history, enabling enhanced PCR testing for a quick diagnosis.

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

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.

Surveillance of antimicrobial resistance and evolving microbial populations in Vermont: 2011-2018.

OBJECTIVE: This study presents trends in organism isolation and antimicrobial resistance in routine microbiology test results from acute-care hospital microbiology laboratories in Vermont. METHODS: Organism identifications and antimicrobial susceptibility test results were captured from acute-care hospital laboratories to monitor geographic and temporal trends in resistance and emerging microbial threats with the free WHONET software. RESULTS: Data were provided from 12 acute care hospital laboratories from 2011 through 2018 for 318,833 isolates from 148,994 patients (70% female, 74% outpatient, and 63% urine). Significant differences (p < 0.05) in age, gender, and antimicrobial susceptibility results (e.g. Escherichia coli and levofloxacin) between outpatient and inpatient isolates were identified with temporal increases in certain species (e.g. Aerococcus urinae) and resistance (e.g. Streptococcus pneumoniae and erythromycin). The use of multi-resistance phenotypes demonstrated significant heterogeneity (p < 0.05) in MRSA strains between facilities, for example Staphylococcus aureus resistant to six priority antimicrobials were found in no critical access hospitals (fewer than 25 inpatient beds) but in all non-critical access hospitals. CONCLUSIONS: Comprehensive electronic surveillance of antimicrobial resistance utilizing routine clinical microbiology data with free software tools offers early recognition and tracking of emerging community and healthcare resistance threats at the local and state level.

Two cases of monkeypox imported to the United Kingdom, September 2018.

In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe the epidemiology and the public health response for the first diagnosed cases outside the African continent since 2003.