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.

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.

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.

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.

Epidemiology of COVID-19 in Prisons, England, 2020.

Using laboratory data and a novel address matching methodology, we identified 734 cases of coronavirus disease in 88 prisons in England during March 16-October 12, 2020. An additional 412 cases were identified in prison staff and household members. We identified 84 prison outbreaks involving 86% of all prison-associated cases.

Infectious disease testing of UK-bound refugees: a population-based, cross-sectional study.

BACKGROUND: The UK, like a number of other countries, has a refugee resettlement programme. External factors, such as higher prevalence of infectious diseases in the country of origin and circumstances of travel, are likely to increase the infectious disease risk of refugees, but published data is scarce. The International Organization for Migration carries out and collates data on standardised pre-entry health assessments (HA), including testing for infectious diseases, on all UK refugee applicants as part of the resettlement programme. From this data, we report the yield of selected infectious diseases (tuberculosis (TB), HIV, syphilis, hepatitis B and hepatitis C) and key risk factors with the aim of informing public health policy. METHODS: We examined a large cohort of refugees (n = 18,418) who underwent a comprehensive pre-entry HA between March 2013 and August 2017. We calculated yields of infectious diseases stratified by nationality and compared these with published (mostly WHO) estimates. We assessed factors associated with case positivity in univariable and multivariable logistic regression analysis. RESULTS: The number of refugees included in the analysis varied by disease (range 8506-9759). Overall yields were notably high for hepatitis B (188 cases; 2.04%, 95% CI 1.77-2.35%), while yields were below 1% for active TB (9 cases; 92 per 100,000, 48-177), HIV (31 cases; 0.4%, 0.3-0.5%), syphilis (23 cases; 0.24%, 0.15-0.36%) and hepatitis C (38 cases; 0.41%, 0.30-0.57%), and varied widely by nationality. In multivariable analysis, sub-Saharan African nationality was a risk factor for several infections (HIV: OR 51.72, 20.67-129.39; syphilis: OR 4.24, 1.21-24.82; hepatitis B: OR 4.37, 2.91-6.41). Hepatitis B (OR 2.23, 1.05-4.76) and hepatitis C (OR 5.19, 1.70-15.88) were associated with history of blood transfusion. Syphilis (OR 3.27, 1.07-9.95) was associated with history of torture, whereas HIV (OR 1521.54, 342.76-6754.23) and hepatitis B (OR 7.65, 2.33-25.18) were associated with sexually transmitted infection. Syphilis was associated with HIV (OR 10.27, 1.30-81.40). CONCLUSIONS: Testing refugees in an overseas setting through a systematic HA identified patients with a range of infectious diseases. Our results reflect similar patterns found in other programmes and indicate that the yields for infectious diseases vary by region and nationality. This information may help in designing a more targeted approach to testing, which has already started in the UK programme. Further work is needed to refine how best to identify infections in refugees, taking these factors into account.

Lack of Secondary Transmission of Ebola Virus from Healthcare Worker to 238 Contacts, United Kingdom, December 2014.

In December 2014, Ebola virus disease (EVD) was diagnosed in a healthcare worker in the United Kingdom after the worker returned from an Ebola treatment center in Sierra Leone. The worker flew on 2 flights during the early stages of disease. Follow-up of 238 contacts showed no evidence of secondary transmission of Ebola virus.

The Epidemiology of Q Fever in England and Wales 2000-2015.

Between 2000 and 2015, 904 cases of acute Q fever were reported in England and Wales. The case dataset had a male to female ratio of 2.5:1, and a median age of 45 years. Two outbreaks were recognised during this time period, and the incidence of sporadic cases was highest across the southwest of England, and Wales. There are limitations in the surveillance system for Q fever, including possible geographical differences in reporting and limited epidemiological data collection. The surveillance system needs to be strengthened in order to improve the quality and completeness of the epidemiological dataset. The authors conclude with recommendations on how to achieve this.

Cyclosporiasis in travellers returning to the United Kingdom from Mexico in 2017: lessons from the recent past to inform the future.

During the summers of 2015 and 2016, the United Kingdom experienced large outbreaks of cyclosporiasis in travellers returning from Mexico. As the source of the outbreaks was not identified, there is the potential for a similar outbreak to occur in 2017; indeed 78 cases had already been reported as at 27 July 2017. Early communication and international collaboration is essential to provide a better understanding of the source and extent of this recurring situation.

Trend analysis of imported malaria in London; observational study 2000 to 2014.

BACKGROUND: We describe trends of malaria in London (2000-2014) in order to identify preventive opportunities and we estimated the cost of malaria admissions (2009/2010-2014/2015). METHODS: We identified all cases of malaria, resident in London, reported to the reference laboratory and obtained hospital admissions from Hospital Episode Statistics. RESULTS: The rate of malaria decreased (19.4[2001]-9.1[2014] per 100,000). Males were over-represented (62%). Cases in older age groups increased overtime. The rate was highest amongst people of Black African ethnicity followed by Indian, Pakistani, Bangladeshi ethnicities combined (103.3 and 5.5 per 100,000, respectively). The primary reason for travel was visiting friends and relatives (VFR) in their country of origin (69%), mostly sub-Saharan Africa (92%). The proportion of cases in VFRs increased (32%[2000]-50%[2014]) and those taking chemoprophylaxis decreased (36%[2000]-14%[2014]). The overall case fatality rate was 0.3%. We estimated the average healthcare cost of malaria admissions to be just over £1 million per year. CONCLUSION: Our study highlighted that people of Black African ethnicity, travelling to sub-Saharan Africa to visit friends and relatives in their country of origin remain the most affected with also a decline in chemoprophylaxis use. Malaria awareness should focus on this group in order to have the biggest impact but may require new approaches.

Pathogens, prejudice, and politics: the role of the global health community in the European refugee crisis.

Involuntary migration is a crucially important global challenge from an economic, social, and public health perspective. The number of displaced people reached an unprecedented level in 2015, at a total of 60 million worldwide, with more than 1 million crossing into Europe in the past year alone. Migrants and refugees are often perceived to carry a higher load of infectious diseases, despite no systematic association. We propose three important contributions that the global health community can make to help address infectious disease risks and global health inequalities worldwide, with a particular focus on the refugee crisis in Europe. First, policy decisions should be based on a sound evidence base regarding health risks and burdens to health systems, rather than prejudice or unfounded fears. Second, for incoming refugees, we must focus on building inclusive, cost-effective health services to promote collective health security. Finally, alongside protracted conflicts, widening of health and socioeconomic inequalities between high-income and lower-income countries should be acknowledged as major drivers for the global refugee crisis, and fully considered in planning long-term solutions.

Cyclospora infection linked to travel to Mexico, June to September 2015.

Cyclospora cayetanensis was identified in 176 returned travellers from the Riviera Maya region of Mexico between 1 June and 22 September 2015; 79 in the United Kingdom (UK) and 97 in Canada. UK cases completed a food exposure questionnaire. This increase in reported Cyclospora cases highlights risks of gastrointestinal infections through travelling, limitations in Cyclospora surveillance and the need for improved hygiene in the production of food consumed in holiday resorts.