A large outbreak of gastrointestinal illness at an open-water swimming event in the River Thames, London.

Open-water swimming is increasingly popular, often in water not considered safe for bathing. Limited evidence exists on the associated health risks. We investigated gastrointestinal illness in 1100 swimmers in a River Thames event in London, UK, to describe the outbreak and identify risk factors. We conducted a retrospective cohort study. Our case definition was swimmers with any: diarrhoea, vomiting, abdominal cramps lasting ⩾48 h, nausea lasting ⩾48 h, with onset within 9 days after the event. We used an online survey to collect information on symptoms, demographics, pre- and post-swim behaviours and open-water experience. We tested associations using robust Poisson regression. We followed up case microbiological results. Survey response was 61%, and attack rate 53% (338 cases). Median incubation period was 34 h and median symptom duration 4 days. Five cases had confirmed microbiological diagnoses (four Giardia, one Cryptosporidium). Wearing a wetsuit [adjusted relative risk (aRR) 6·96, 95% confidence interval (CI) 1·04-46·72] and swallowing water (aRR 1·42, 95% CI 1·03-1·97) were risk factors. Recent river-swimming (aRR 0·78, 95% CI 0·67-0·92) and age >40 years (aRR 0·83, 95% CI 0·70-0·98) were protective. Action to reduce risk of illness in future events is recommended, including clarification of oversight arrangements for future swims to ensure appropriate risk assessment and advice is provided.

The prospective evaluation of the TB strain typing service in England: a mixed methods study.

BACKGROUND: In response to rising TB notification rates in England, universal strain typing was introduced in 2010. We evaluated the acceptability, effectiveness and cost-effectiveness of the TB strain typing service (TB-STS). METHODS: We conducted a mixed-methods evaluation using routine laboratory, clinic and public health data. We estimated the effect of the TB-STS on detection of false positive Mycobacterium tuberculosis diagnoses (2010-2012); contact tracing yield (number of infections or active disease per pulmonary TB case); and diagnostic delay. We developed a deterministic age-structured compartmental model to explore the effectiveness of the TB-STS, which informed a cost-effectiveness analysis. RESULTS: Semi-structured interviews explored user experience. Strain typing identified 17 additional false positive diagnoses. The TB-STS had no significant effect on contact tracing yield or diagnostic delay. Mathematical modelling suggested increasing the proportion of infections detected would have little value in reducing TB incidence in the white UK-born population. However, in the non-white UK-born and non-UK-born populations, over 20 years, if detection of latent infection increases from 3% to 13% per year, then TB incidence would decrease by 11%; reducing diagnostic delay by one week could lead to 25% reduction in incidence. The current TB-STS was not predicted to be cost-effective over 20 years (£95 628/quality-adjusted life-years). Interviews found people had mixed experiences, but identified broader benefits, of the TB-STS. CONCLUSIONS: To reduce costs, improve efficiency and increase effectiveness, we recommend changes to the TB-STS, including discontinuing routine cluster investigations and focusing on reducing diagnostic delay across the TB programme. This evaluation of a complex intervention informs the future of strain typing in the era of rapidly advancing technologies.

Selection of population controls for a Salmonella case-control study in the UK using a market research panel and web-survey provides time and resource savings.

Timely recruitment of population controls in infectious disease outbreak investigations is challenging. We evaluated the timeliness and cost of using a market research panel as a sampling frame for recruiting controls in a case-control study during an outbreak of Salmonella Mikawasima in the UK in 2013. We deployed a web-survey by email to targeted members of a market research panel (panel controls) in parallel to the outbreak control team interviewing randomly selected public health staff by telephone and completing paper-based questionnaires (staff controls). Recruitment and completion of exposure history web-surveys for panel controls (n = 123) took 14 h compared to 15 days for staff controls (n = 82). The average staff-time cost per questionnaire for staff controls was £13·13 compared to an invoiced cost of £3·60 per panel control. Differences in the distribution of some exposures existed between these control groups but case-control studies using each group found that illness was associated with consumption of chicken outside of the home and chicken from local butchers. Recruiting market research panel controls offers time and resource savings. More rapid investigations would enable more prompt implementation of control measures. We recommend that this method of recruiting controls is considered in future investigations and assessed further to better understand strengths and limitations.

No evidence of transmission from an acute case of hepatitis A in a foodhandler: follow-up of almost 1,000 potentially exposed individuals, London, United Kingdom, April 2012.

Identification of acute hepatitis A virus (HAV) infection in a foodhandler in a London hotel led to a large incident response. We identified three potentially exposed groups: hotel staff who had regularly consumed food prepared by the case and shared toilet facilities with the case, patients who shared the same hospital ward as the case and hotel guests who consumed food prepared by the case. We arranged post-exposure HAV vaccination for all 83 potentially exposed hotel staff and all 17 patients. We emailed 887 guests advising them to seek medical care if symptomatic, but did not advise vaccination as it was too late to be effective for most guests. Through the International Health Regulations national focal points and the European Union Early warning and response system (EWRS), we communicated the details of the incident to public health agencies and potential risk of HAV transmission to international guests. Potentially exposed hotel staff and guests were asked to complete an online or telephone-administered questionnaire 50 days following possible exposure, to identify any secondary cases. Survey response was low, with 155 responses from guests and 33 from hotel staff. We identified no secondary cases of HAV infection through follow-up.

Investigating an outbreak of Clostridium perfringens gastroenteritis in a school using smartphone technology, London, March 2013.

On 22 March 2013, 150 of 1,255 students (13­17 years) and staff at a school in London reported gastrointestinal symptoms; onset peaked 8 to 12 hours after a lunch served in the school on 21 March. We performed a retrospective cohort study of all students and staff. We defined cases as school attenders on 20 and 21 March with onset of gastrointestinal symptoms between 20 and 23 March. We tested food, environmental and stool samples of cases for common pathogens and bacterial toxins. We administered an online questionnaire via email, encouraging the use of smartphones to respond, to measure risk of illness for food items eaten at school on 20 and 21 March. Survey response was 45%. Adjusted risk ratios were generated in a multivariable analysis. Those who ate chicken balti on 21 March were 19.3 times more likely to become ill (95% confidence interval: 7.3­50.9). Clostridium perfringens was detected in all 19 stool samples collected. Within eight school hours of its launch, 412 of 561 (73%) responders had completed the survey. Hygienic standards in the kitchen were satisfactory. The investigation was done rapidly due to smartphone technology and we recommend considering this technology in future outbreaks.

Salmonella enterica serovar Enteritidis phage type 4 outbreak associated with eggs in a large prison, London 2009: an investigation using cohort and case/non-case study methodology.

In September 2009, an outbreak of Salmonella enterica serovar Enteritidis affected 327 of 1419 inmates at a London prison. We applied a cohort design using aggregated data from the kitchen about portions of food distributed, aligned this with individual food histories from 124 cases (18 confirmed, 106 probable) and deduced the exposures of those remaining well. Results showed that prisoners eating egg cress rolls were 26 times more likely to be ill [risk ratio 25.7, 95% confidence interval (CI) 15.5-42.8, P<0.001]. In a case/non-case multivariable analysis the adjusted odds ratio for egg cress rolls was 41.1 (95% CI 10.3-249.7, P<0.001). The epidemiological investigation was strengthened by environmental and microbiological investigations. This paper outlines an approach to investigations in large complex settings where aggregate data for exposures may be available, and led to the development of guidelines for the management of future gastrointestinal outbreaks in prison settings.

Outbreak investigation and case-control study: penta-resistant Salmonella Typhimurium DT104 associated with biltong in London in 2008.

In August 2008 an outbreak of Salmonella Typhimurium DT104 occurred in South West London. Sixteen cases were identified with a particular multilocus variable number tandem repeat analysis (MLVA) pattern. In a matched case-control study 14 primary cases were included. These were defined as individuals with gastrointestinal symptoms and Salmonella Typhimurium DT104 isolated from a stool specimen, with a characteristic antibiotic resistance profile and MLVA pattern, and diagnosed in a local laboratory. Four controls per case were matched on age, gender and area of residence. Cases were 26 times more likely than controls to have eaten beef biltong, a South African speciality meat product (odds ratio 25·83, 95% confidence interval 4·92­135·59, P < 0·01). Although environmental investigation failed to identify Salmonella in the food product we conclude that beef biltong consumption led to this outbreak. This conclusion has importance in informing the ongoing risk assessment relating to uncontrolled foodstuffs.

The case-cohort design in outbreak investigations.

The use of the case-cohort design for outbreak investigations has been limited. Here we discuss its strengths and limitations based on real and fictitious examples. The case-cohort is a case­control study where controls are sampled from the initial population at risk, and may thus include both cases and non-cases. An advantage of the design, compared to traditional case-control studies, is that risk ratios can easily be obtained directly from the cross-product of exposed and unexposed cases and controls (rare disease assumption is not required). We illustrate this in the context of point source gastrointestinal outbreaks and in field studies on vaccine effectiveness. The design is also useful to investigate multiple outcomes with a unique sample of controls or to test hypotheses when different case-definitions (from the most sensitive to the most specific) are used for a particular outcome. Strengths and limitations are presented, and discussed in the context of outbreak investigations.

Recent trends in tuberculosis in children in London.

BACKGROUND: Childhood tuberculosis (TB) represents a sentinel event of recent transmission and is an indication of the effectiveness of prevention and control interventions. We analysed the trends in the epidemiology of TB in children in London aged 0-14 years between 1999 and 2006. METHODS: Data were extracted from the Enhanced TB Surveillance System. RESULTS: Between 1999 and 2006, there were 1370 cases of TB in children. Incidence was higher in older children and in girls. The incidence rates in London Boroughs varied from 0.4/100,000 to 32.7/100,000. Between 1999 and 2006, Black-Africans comprised 49.2% of all TB cases in children, children from the Indian Subcontinent 21.8% and Whites 8.5%. The proportion of cases born in the UK averaged 52.4% during this period. Of non-UK-born children 79.3% were diagnosed with TB within 5 years of entry. CONCLUSIONS: Ethnicity, country of birth and age are important risk factors for development of. With an overall TB incidence in London exceeding 40/100,000, universal BCG immunization of all neonates should be considered across all London boroughs.

Large outbreak of isoniazid-monoresistant tuberculosis in London, 1995 to 2006: case-control study and recommendations.

We conducted a case­control study to examine risk factors for isoniazid-monoresistant Mycobacterium tuberculosis in an ongoing outbreak in London. Cases were defined as individuals with an isoniazid-monoresistant strain diagnosed from 1995 to the third quarter of 2006 with an indistinguishable restriction fragment length polymorphism (RFLP) or mycobacterial interspersed repetitive unit (MIRU)-variable number tandem repeats (VNTR) pattern who were resident in or had epidemiological links with London. Controls were all other individuals reported with tuberculosis to the Health Protection Agency London regional epidemiology unit or the HPA London TB Register during 2000 to 2005. Of 293 cases, 153 (52%) were sputum smear-positive compared with 3,266 (18%) of controls. Cases were more likely to be young adults (aged between 15 and 34 years), born in the United Kingdom (OR: 2.4; 95% CI: 1.7­3.4) and of white (OR: 2.9; 95% CI: 1.8­4.8) or black Caribbean (OR: 12.5; 95% CI: 7.7­20.4) ethnicity, a prisoner at the time of diagnosis (OR: 20.2; 95% CI: 6.7­60.6), unemployed (OR: 4.1; 95% CI: 3.0­5.6), or a drug dealer or sex worker (OR: 187.1; 95% CI: 28.4­1,232.3). A total of 113 (39%) of cases used drugs and 54 (18%) were homeless. Completion of treatment gradually improved in cases from 55% among those diagnosed up to the end of 2002 compared with 65% by the end of 2006. Treatment completion increased from 79% to 83% in controls from 2000 to 2005. There are complex social challenges facing many cases in this outbreak that need to be addressed if medical interventions are to be successful.

Early spread of the 2009 influenza A(H1N1) pandemic in the United Kingdom--use of local syndromic data, May-August 2009.

Following the confirmation of the first two cases of pandemic influenza on 27 April 2009 in the United Kingdom (UK), syndromic surveillance data from the Health Protection Agency (HPA)/QSurveillance and HPA/NHS Direct systems were used to monitor the possible spread of pandemic influenza at local level during the first phase of the outbreak. During the early weeks, syndromic indicators sensitive to influenza activity monitored through the two schemes remained low and the majority of cases were travel-related. The first evidence of community spread was seen in the West Midlands region following a school-based outbreak in central Birmingham. During the first phase several Primary Care Trusts had periods of exceptional influenza activity two to three weeks ahead of the rest of the region. Community transmission in London began slightly later than in the West Midlands but the rates of influenza-like illness recorded by general practitioners (GPs) were ultimately higher. Influenza activity in the West Midlands and London regions peaked a week before the remainder of the UK. Data from the HPA/NHS Direct and HPA/QSurveillance systems were mapped at local level and used alongside laboratory data and local intelligence to assist in the identification of hotspots, to direct limited public health resources and to monitor the progression of the outbreak. This work has demonstrated the utility of local syndromic surveillance data in the detection of increased transmission and in the epidemiological investigation of the pandemic and has prompted future spatio-temporal work.

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo.

A hurdle facing DNA vaccine development is the ability to generate strong immune responses systemically and at local immune sites. We report a novel systemically administered DNA vaccination strategy using intramuscular codelivery of CCL27 or CCL28, which elicited elevated peripheral IFN-gamma and antigen-specific IgG while driving antigen-specific T-cell secretion of cytokine and antibody production in the gut-associated lymphoid tissue and lung. This strategy resulted in induction of long-lived antibody responses that neutralized influenza A/PR8/34 and protected mice from morbidity and mortality associated with a lethal intranasal viral challenge. This is the first example of the use of CCL27 and CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting further examination of this approach for manipulation of vaccine-induced immunity impacting both quality and phenotype of responses.

Studies on the sensitization of animals with simple chemical compounds. 13. Sensitization of guinea pigs with picric acid.

A method of establishing regular and intense sensitivity to picric acid is described, based upon an initial sensitization by a "split-adjuvant" technique in which the intradermal injection of mycobacteria in paraffin oil precedes or follows the administration of allergen to the same sites. When subsequent contact applications of picric acid are later made, the degree of sensitivity rises in steps such that reactivity occurs in tests made with low concentrations of picric acid, in the range of 0.06-0.006% but varying somewhat from one experiment to another. This heightening of picric acid reactivity represents an anamnestic response in the area of delayed hypersensitivity. The characteristics of contact reactions to the weak allergen, picric acid, differ from those encountered with covalently binding haptens, PCI and DNCB. A slow evolution from an initial micropapular reaction to full reaction requires about 3 days, leading often to a micaceous scale, with histological evidence of vesiculation even while the reaction is still feeble, and to an infiltrate containing a significant number of polymorphonuclear leukocytes. Substitution of an emulsion of picric acid in complete Freund's adjuvant as a priming experience proved to be much less efficient. The split-adjuvant technique offers a general plan for sensitizing with weak allergens. Indeed, technically, sensitization can be acquired even when, for priming, the allergen is applied topically over intradermal depots of mycobacteria in paraffin oil. Compatibility between sensitizer and adjuvant is not required.

Pandemic (H1N1) 2009 virus outbreak in a school in London, April-May 2009: an observational study.

On 29 April 2009, an imported case of pandemic (H1N1) 2009 virus infection was detected in a London school. As further cases, pupils and staff members were identified, school closure and mass prophylaxis were implemented. An observational descriptive study was conducted to provide an insight into the clinical presentation and transmission dynamics in this setting. Between 15 April and 15 May 2009, 91 symptomatic cases were identified: 33 were confirmed positive for pandemic (H1N1) 2009 virus infection; 57 were tested negative; in one the results were unavailable. Transmission occurred first within the school, and subsequently outside. Attack rates were 2% in pupils (15% in the 11-12 years age group) and 17% in household contacts. The predominant symptoms were fever (97%), respiratory symptoms (91%), and sore throat (79%). Limited spread in the school may have been due to a combination of school closure and mass prophylaxis. However, transmission continued through household contacts to other schools.

Pandemic (H1N1) 2009 influenza in the UK: clinical and epidemiological findings from the first few hundred (FF100) cases.

The UK was one of few European countries to document a substantial wave of pandemic (H1N1) 2009 influenza in summer 2009. The First Few Hundred (FF100) project ran from April-June 2009 gathering information on early laboratory-confirmed cases across the UK. In total, 392 confirmed cases were followed up. Children were predominantly affected (median age 15 years, IQR 10-27). Symptoms were mild and similar to seasonal influenza, with the exception of diarrhoea, which was reported by 27%. Eleven per cent of all cases had an underlying medical condition, similar to the general population. The majority (92%) were treated with antiviral drugs with 12% reporting adverse effects, mainly nausea and other gastrointestinal complaints. Duration of illness was significantly shorter when antivirals were given within 48 h of onset (median 5 vs. 9 days, P=0.01). No patients died, although 14 were hospitalized, of whom three required mechanical ventilation. The FF100 identified key clinical and epidemiological characteristics of infection with this novel virus in near real-time.

High rate of transmission among contacts in large London outbreak of isoniazid mono-resistant tuberculosis.

BACKGROUND: For a continuing London outbreak of isoniazid mono-resistant tuberculosis (TB), we aimed to determine transmission rates and risk factors for contacts of early cases, in order to inform future guidance on contact tracing. METHODS: Paper-based proformas were completed by TB nurses, and then analysed using EpiInfo/SAS statistical software. RESULTS: Forty community contacts (11%) became cases, 45 (13%) were recommended chemoprophylaxis and 270 (76%) were discharged clear of infection. The highest transmission rate was among contacts exposed to two or more cases (29% became cases) and close contacts of sputum smear-positive cases (22%). Other risk factors were being male and exposure to drug-using cases or cases with prison links. The number needed to be screened (NNS) to detect one case was lowest [5 (95% CI: 4-8)] for contacts of sputum smear-positive pulmonary cases, although the NNS was still only 20 (95% CI:8-72) for casual contacts of smear-positive cases. CONCLUSIONS: Transmission of disease to contacts was high (11%) compared with other documented outbreaks (0.7-2%). The results support recommended guidelines for contact tracing but also provide grounds to recommend, for outbreak cases, screening of casual contacts of smear-positive cases and contacts exposed to more than one case, drug users or prisoners.

The international follow-up of individuals potentially exposed to polonium-210 in London 2006.

OBJECTIVES: Following a death from polonium-210 ((210)Po), contamination was found at several sites in London. This paper describes the UK Health Protection Agency's follow-up and assessment of individuals resident overseas who were potentially exposed to (210)Po. STUDY DESIGN: Descriptive follow-up study. METHODS: Individuals were classified into three exposure groups (higher, lower and unknown). Presence and degree of internal contamination were measured by 24-h urinary (210)Po activity (mBq/day). Results over 30mBq/day were taken to indicate probable contact with (210)Po in this incident. Dose assessments were conducted to determine degree of exposure and to identify individuals requiring further follow-up. RESULTS: Overall, 664 potentially exposed persons from 52 countries and territories were identified. Of these, 157 (24%) were in the higher exposure category, and urinary measurements were reported for 31% (48/157). Results for 19% (9/48) of those at higher exposure were more than 30mBq/day. For those at lower exposure, the percentage was 4% (3/68). Results above 30mBq/day were significantly more likely to be reported for the higher exposure category than the lower exposure category (Fisher's exact test P=0.010). Reported dose assessments suggested that identified individuals were not at increased health risk in the long term. Challenges and practical lessons were identified during the investigation. CONCLUSION: The results suggest that it is unlikely that any overseas resident had significant internal contamination with (210)Po. However, this incident clearly demonstrated the scale of international involvement likely to be necessary in other public health emergencies in large cities. The lessons identified have implications for the international health community, particularly with regard to the follow-up of individuals exposed to radiation in one country who then travel to another.

Assessing public health risk in the London polonium-210 incident, 2006.

OBJECTIVES: Mr Alexander Litvinenko died in a London hospital on 23 November 2006, allegedly from poisoning with the radionuclide polonium-210 ((210)Po). Associated circumstances required an integrated response to investigate the potential risk of internal contamination for individuals exposed to contaminated environments. STUDY DESIGN: Descriptive study. METHODS: Contaminated locations presenting a potential risk to health were identified through environmental assessment by radiation protection specialists. Individuals connected with these locations were identified and assessed for internal contamination with (210)Po. RESULTS: In total, 1029 UK residents were identified, associated with the 11 most contaminated locations. Of these, 974 were personally interviewed and 787 were offered urine tests for (210)Po excretion. Overall, 139 individuals (18%) showed evidence of probable internal contamination with (210)Po arising from the incident, but only 53 (7%) had assessed radiation doses of 1mSv or more. The highest assessed radiation dose was approximately 100mSv. CONCLUSIONS: Although internal contamination with (210)Po was relatively frequent and was most extensive among individuals associated with locations judged a priori to pose the greatest risk, a high degree of assurance could be given to UK and international communities that the level of health risk from exposure to the radionuclide in this incident was low.

Audit of laboratory diagnostic methods for syphilis in England and Wales.

OBJECTIVES: The number of cases of infectious syphilis is increasing rapidly across England and Wales. Concern has been expressed about diagnostic delay and its potential impact on patient care. A standard operating procedure for the serological diagnosis of syphilis has recently been developed by the Health Protection Agency. This study aimed to audit clinical and laboratory practice in England and Wales against this standard. METHODS: All microbiology departments, genitourinary medicine (GUM) clinics and antenatal clinics in England and Wales were invited to complete a web-based questionnaire. RESULTS: The overall response rate was 76%. Practices varied between laboratories. The proportion of microbiology departments performing enzyme immunoassay (EIA), Treponema pallidum particle agglutination assay/T pallidum haemagglutination assay, rapid plasma reagin/Venereal Disease Reference Laboratory and EIA IgM were 94%, 34%, 41% and 10%, respectively. Of these, 57% only perform a single screening assay. The turnaround time for negative results was less than 1 week for 84% of microbiology departments. For positive samples, turnaround times varied from less than 1 week to 6-8 weeks, with 19% of GUM clinics reporting turnaround times of over 3 weeks. Notably, 26% of GUM clinics and 6% of antenatal clinics reported that delays in turnaround time had adversely affected patient management in the past year. CONCLUSION: This study suggests that there is significant room to improve laboratory turnaround times for the diagnosis of syphilis in England and Wales, and such improvements would be a positive step in limiting the spread of infection and of congenital syphilis.

HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions.

The hepatitis B virus (HBV) X gene product trans-activates viral and cellular genes. The X protein (pX) does not bind independently to nucleic acids. The data presented here demonstrate that pX entered into a protein-protein complex with the cellular transcriptional factors CREB and ATF-2 and altered their DNA binding specificities. Although CREB and ATF-2 alone did not bind to the HBV enhancer element, a pX-CREB or pX-ATF-2 complex did bind to the HBV enhancer. Thus, the ability of pX to interact with cellular factors broadened the DNA binding specificity of these regulatory proteins and provides a mechanism for pX to participate in transcriptional regulation. This strategy of altered binding specificity may modify the repertoire of genes that can be regulated by transcriptional factors during viral infection.