Universal HIV testing in London tuberculosis clinics: a cluster randomised controlled trial.

We assessed whether implementation of a combination of interventions in London tuberculosis clinics raised the levels of HIV test offers, acceptance and coverage. A stepped-wedge cluster randomised controlled trial was conducted across 24 clinics. Interventions were training of clinical staff and provision of tailor-made information resources with or without a change in clinic policy from selective to universal HIV testing. The primary outcome was HIV test acceptance amongst those offered a test, before and after the intervention; the secondary outcome was an offer of HIV testing. Additionally, the number and proportion of HIV tests among all clinic attendees (coverage) was assessed. 1,315 patients were seen in 24 clinics. The offer and coverage of testing rose significantly in clinics without (p = 0.002 and p = 0.004, respectively) and with an existing policy of universal testing (p = 0.02 and p = 0.04, respectively). However, the level of HIV test acceptance did not increase in 18 clinics without routine universal testing (p = 0.76) or the six clinics with existing universal testing (p = 0.40). The intervention significantly increased the number of HIV tests offered and proportion of participants tested, although acceptance did not change significantly. However, the magnitude of increase is modest due to the high baseline coverage.

School closures and student contact patterns.

To determine how school closure for pandemic (H1N1) 2009 affected students' contact patterns, we conducted a retrospective questionnaire survey at a UK school 2 weeks after the school reopened. School closure was associated with a 65% reduction in the mean total number of contacts for each student.

Surveillance of tuberculosis (TB) cases attributable to relapse or reinfection in London, 2002-2015.

Recurrence of TB in an individual can occur due to relapse of the same strain or reinfection by a different strain. The contribution of reinfection and relapse to TB incidence, and the factors associated with each are unknown. We aimed to quantify and describe cases attributable to relapse or reinfection, and identify associated risk factors in order to reduce recurrence. We categorised recurrent TB cases from notifications in London (2002-2015) as relapse or reinfection using molecular (MIRU VNTR strain type) and epidemiological information (hierarchical approach using time since notification, site of disease and method of case finding). Factors associated with each outcome were determined using logistic regression in Stata Version 13.1 (2009-2015 only). Of 43,465 TB cases, 1.4% (618) were classified as relapse and 3.8% (1,637) as reinfection. The proportion with relapse decreased from 2002 (2.3%) to 2015 (1.3%), while the proportion of reinfection remained around 4%. Relapse was more common among recent migrants (<1 year, odds ratio (OR) = 1.99, p = 0.005), those with a social risk factor (OR = 1.51, p = 0.033) and those with central nervous system, spinal, miliary or disseminated TB (OR = 1.75, p = 0.001). Reinfection was more common among long term migrants (>11 years, OR = 1.67, p = <0.001), those with a social risk factor (OR = 1.96, p = <0.001) and within specific areas in London. Patients with social risk factors were at increased risk of both relapse and reinfection. Characterising those with relapsed disease highlights patients at risk and factors associated with reinfection suggest groups where transmission is occurring. This will inform TB control programs to target appropriate treatment and interventions in order to reduce the risk of recurrence.

Presentation and healthcare delays among people with tuberculosis in London, and the impact on treatment outcome.

Background: A quarter of London's pulmonary tuberculosis (TB) patients have over 4 months of delay. Late diagnosis increases disease severity and the risk of transmission. We aim to classify delays, identify associated risk factors and assess treatment outcome. Methods: We conducted a retrospective cohort study using London surveillance data, 2012-2018 on adults aged ≥18 years with pulmonary TB. We defined presentation delay (days from symptom onset to first healthcare visit) and healthcare delay (first healthcare visit to treatment commencement) as dichotomous variables; positive delay being days equal or greater than the third quartile. We applied logistic regression models to identify risk factors associated with delays and treatment outcome at 12 months. Results: Of 7216 people, 4539 reported presentation and 5193 healthcare delays. The third quartiles for presentation and healthcare delay were 84 and 61 days, respectively. Presentation delay was associated with female sex (adjusted OR (aOR)=1.21; 95% CI 1.04 to 1.39), increasing age (aOR=1.004; 95% CI 1.001 to 1.008), white compared to Asian ethnicity (aOR=1.35; 95% CI 1.12 to 1.62), previous imprisonment (aOR=1.66; 95% CI 1.22 to 2.26) and alcohol misuse (aOR=1.44; 95% CI 1.04 to 1.89). Healthcare delay was associated with female sex (aOR=1.39; 95% CI 1.21 to 1.59), increasing age (aOR=1.014; 95% CI 1.009 to 1.018) and white ethnicity (aOR=1.41; 95% CI 1.19 to 1.68). 16% of 5678 people with known outcome did not complete treatment. Neither delay was associated with non-completion (p value <0.05). Conclusions: Female, white and older people with TB were more likely to experience both presentation and healthcare delays. Social risk factors were also associated with delay in presentation. Early diagnosis and treatment remain critical to reduce transmission, regardless of whether delay affected completion.

XDR-TB transmission in London: Case management and contact tracing investigation assisted by early whole genome sequencing.

OBJECTIVES: We describe the first published cluster of extensively drug resistant Tuberculosis (XDR-TB) in the UK and show how early whole genome sequencing (WGS) of Mtb can assist in case management and contact investigations. METHODS: We describe the contact tracing investigation undertaken after the presentation of an adult with XDR-TB. Active cases were treated with an XDR-TB drug regimen and contacts underwent a programme of follow-up for 2 years. All isolates of Mycobacterium tuberculosis (Mtb) were assessed early using whole genome sequencing (WGS) as well as routine drug susceptibility testing (DST). RESULTS: Thirty-three contacts were screened. In the first year one confirmed and one probable case were identified through contact tracing. A further possible case was identified through epidemiological links. Two confirmed cases were identified through WGS 2 years later. Twenty-five (80%) contacts without evidence of tuberculosis were adherent to 1 year of follow-up and 14 (45%) were adherent to 2 years of follow-up. WGS of Mtb was used to guide drug choices, rapidly identify transmission events, and alter public health management. CONCLUSION: WGS of Mtb enabled rapid effective individualized treatment and facilitated public health interventions by early identification of transmission events.

An audit of the laboratory diagnosis of cryptosporidiosis in England and Wales.

To assess the level of practice consistent with UK national standards for Cryptosporidium testing, an audit was performed of 156 publicly funded clinical microbiology laboratories in England and Wales between August 2013 and April 2014. Responses were received from 85 (54 %) laboratories. First line diagnostic methods used were mainly microscopy with modified Ziehl-Neelsen (mZN) or auramine phenol (AP) staining (68/85, 80 %), enzyme immunoassays (EIAs) (16/85, 19 %) or in-house PCR (1/85, 1 %). The use of EIAs was more widespread than reported previously. Various methods were used for confirmation of positive EIA reactions and laboratories frequently resorted to sending samples to the national reference laboratory for this purpose, indicating that guidance is required for performance monitoring and confirmation of positive reactions. Laboratory positivity rates were related to the diagnostic test used, with highest median rates reported by those using PCR, EIAs or AP microscopy, and the lowest by those using mZN microscopy. One-third of responding laboratories (28/85, 33 %) routinely tested all stools for Cryptosporidium. However, 16 (19 %) laboratories used stool consistency to decide whether to test for this parasite. Other selection criteria included patient age (n = 18; 21 % laboratories), history or clinical details (n = 40; 47 %), duration of hospitalization (n = 18; 21 %) or clinician requests (n = 25; 29 %). To encourage laboratories to test all stools submitted for the investigation of diarrhoeal illness for Cryptosporidium, revision of the guidance in the national standards is under way. This will enable improved assessment of the burden of illness and ability to monitor outbreaks, and measure changes in reported cases.

Asymptomatic carriage of protozoan parasites in children in day care centers in the United kingdom.

Point prevalence of Cryptosporidium and Giardia carriage among 230 asymptomatic preschool children attending day-care facilities was 1.3% (95% CI: 0.3%-3.8%) for each parasite, with no dual infections. Cryptosporidium oocysts were detected by immunomagnetic separation and immunofluorescence microscopy and genotyped: one isolate was Cryptosporidium hominis, the other 2 being skunk and cervine genotypes, rarely found in symptomatic human infection.

Prevalence of nasopharyngeal carriage of pneumococcus in preschool children attending day care in London.

OBJECTIVE: To estimate the prevalence of nasopharyngeal (NP) carriage of pneumococcus (Streptococcus pneumoniae) and describe the antibiotic resistance patterns and serotypes in young children attending group day care in London. DESIGN AND SUBJECTS: Cross-sectional survey of attendees at a sample of registered child day care centres (CDCCs) in a London borough. SETTING: Urban setting with a socially and culturally diverse population. METHODS AND OUTCOMES: 19 CDCCs (13% of total) participated between March and November 2003. A single NP swab was required from each child, and parents completed a questionnaire about their child's health and attendance at day care. WHO methodology for pneumococcal carriage studies was followed. RESULTS: 30% of parents consented. 234 swabs were collected from children aged 6 months to 5 years. 53% were boys and 81% were white. 120 children (51%, 95% CI 45% to 58%) carried pneumococci in their nasopharynx. None of the isolates were resistant to penicillin (upper CL 3%). 21 isolates were resistant to erythromycin (17.5%, 95% CI 11% to 25.5%). 68 isolates (57%) were serotypes included in the 7-valent conjugate vaccine. Non-white children had a lower prevalence of carriage (27% vs 58%). CONCLUSION: The prevalence of pneumococcal NP carriage was high. The penicillin resistance rate is lower than in many other countries and may reflect a decrease in community antibiotic prescribing in the UK. Monitoring circulating serotypes is important in the context of recent changes to the vaccination policy. Further study is required to explore the association with ethnicity and risk factors for antibiotic resistance.