Tuberculosis in London Annual review (2015 data) Data from 2000 to 2015

Transcription

1 Tuberculosis in London Annual review (2015 data) Data from 2000 to 2015

2 About Public Health England Public Health England exists to protect and improve the nation s health and wellbeing, and reduce health inequalities. We do this through world-class science, knowledge and intelligence, advocacy, partnerships and the delivery of specialist public health services. We are an executive agency of the Department of Health, and are a distinct delivery organisation with operational autonomy to advise and support government, local authorities and the NHS in a professionally independent manner. Public Health England, Wellington House, Waterloo Road, London SE1 8UG Tel: Facebook: About the Field Epidemiology Service The Field Epidemiology Service (FES) supports PHE centres and partner organisations through the application of epidemiological methods to inform public health action. FES does this in two main ways: first by providing a flexible expert resource, available as and when needed, to undertake epidemiological investigations for key health protection work, and second through the expert analysis, interpretation and dissemination of surveillance information to PHE centres, local health partners, service providers and commissioners of services. Within the FES network, excellence and innovation is encouraged. We foster academic collaborations and take active part and lead in research, development and training. You can contact your local FES team at fes.seal@phe.gov.uk Prepared by: Field Epidemiology Service For queries relating to this document, please contact: ltbr.support@phe.gov.uk Crown copyright 2017 You may re-use this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence v3.0. To view this licence, visit OGL or psi@nationalarchives.gsi.gov.uk. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. Published January 2017 PHE gateway number:

3 Contents About the Field Epidemiology Service 2 About Public Health England 2 Notes on the report 5 Executive summary 6 1. TB notifications and incidence Laboratory confirmation of TB TB transmission Delay from onset of symptoms to start of treatment TB outcome in drug sensitive cohort Drug resistant TB (including outcomes in the drug resistant cohort) TB in under-served populations HIV testing & coinfection, hospitalisation, directly observed therapy and BCG Latent TB infection testing and treatment 35 Discussion 36 Conclusion 37 References 39 Appendix A: Description of data sources and definitions 40 Appendix B: TB among London residents 42 Appendix C: Local authority TB epidemiological summaries 45 The data presented in this report is correct as at August

4 Acknowledgements We are grateful to all those who contribute information on tuberculosis cases in London, including nurses, physicians, microbiologists, scientists, outreach and social care and administrative staff. We also acknowledge colleagues at the Public Health England (PHE) National Mycobacterium Reference Laboratory for information on culture confirmation and drug susceptibility testing. Further thanks are due to the national Centre for Infectious Disease Surveillance and Control for matching the clinical and laboratory information, Jacqui Carless, Lamya Kanfoudi and Neil Billingham for their work supporting the London TB Register, and the PHE London Health Protection Team staff. Authors This report was prepared by Daniele Curtis, Neil Macdonald and Charlotte Anderson of the Field Epidemiology Service (South East and London team), National Infection Service, PHE. Suggested citation Public Health England. (January 2017) Tuberculosis in London: Annual review (2015 data), Public Health England: London. 4

5 Notes on the report Intended audience This report is aimed at healthcare professionals involved in the diagnosis and/or treatment of TB patients, commissioners involved in planning and financing TB services, public health professionals working in the control of TB or health of at-risk populations, researchers with an interest in TB, and government and non-governmental organisations working in the field of TB. In particular we aim to update the London TB Control Board and London clinical leadership group. Aim of report This report describes the recent epidemiology of TB in London, providing an update on local trends, and identifying areas of high burden of disease, at-risk population groups, and opportunities for interventions and prevention of future cases. Data sources This report presents detailed data on TB case notifications made to the London TB Register and Enhanced Tuberculosis Surveillance system (ETS) in England to the end of Data from notifications made to ETS from 2000 is updated annually to take into account denotifications, late notifications and other updates. The data presented in the current year s report supersedes data in previous reports. Experimental BCG coverage data for areas with universal BCG vaccination is presented using the Cover of Vaccination Evaluated Rapidly (COVER) programme data. Other data displays The national report presenting recent epidemiology of TB in England is available at B_annual_report_2016.pdf. Additional high-level data on TB notifications in the UK to the end of 2015, and breakdowns by country, can be found in the Official Statistic for TB, Reports of cases of tuberculosis to enhanced tuberculosis surveillance systems: United Kingdom, 2000 to This is available at 5

6 As part of the Collaborative TB Strategy for England , a suite of TB Strategy Monitoring Indicators have been developed ( Collaborative_TB_Strategy_for_England_2015_2020_.pdf). Data for indicators which are presented at Upper Tier Local Authority and Clinical Commissioning Group can be found at Executive summary In 2015, 2,269 cases of tuberculosis (TB) were notified among London residents; a rate of 26 per 100,000 population. As seen across England, there has been a year-on-year decline in the rate of TB in London since This was a 12% decrease from the rate observed in 2014 and a 38% decrease since London still has the highest rate in the country, accounting for 39% of the 5,758 cases in England. 1 The highest numbers and rates of TB were reported among residents of Newham and Brent local authorities, though they have decreased substantially in these areas in recent years. The majority of the decline has been in the rate among those born abroad, which has halved since the peak in 2005, with most of the decrease since The TB rate decreased in the non-uk born London population by 13% relative to From the reduction in non-uk born cases was mostly due to falling numbers among very recent entrants (entered the UK within previous two years). Since then, however, the reduction in cases has been driven by decreasing numbers among those who had arrived 2-5 years previously. In London, this trend was predominantly driven by decreasing cases among young Indian-born adults who had arrived within the previous five years. London residents of Indian ethnicity still experienced the highest rate of TB, although rates in this population have decreased since This reflects trends in country of birth: 26% of non-uk born patients were born in India, but numbers decreased by 18% since 2014, and 39% since This was the third consecutive year of a small but sustained decrease in TB incidence among the UK born population. The TB rate in the UK born population decreased by 12% compared to However, at 7.9 per 100,000, the rate in the UK born population of London remains more than twice the national average. 1 Half of all TB patients had pulmonary disease, and where known, 45% were sputum smear positive. Only 59% of cases were culture confirmed, although this was higher 6

7 among those with pulmonary disease (74%). As in recent years, only a very small proportion of patients had a previous history of TB. The rate of TB in UK born children under 15 years of age in London (4.4 per 100,000) and the proportion of cases that were clustered with at least one other case in London (47% in 2015 using 24 loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats) both decreased in 2015, suggesting a reduction in TB transmission within London. Among London residents with pulmonary TB, the median time between symptom onset and treatment start was 64 days. This was an improvement from 2014, and was eight days shorter than the median delay for England overall in The proportion of pulmonary TB cases starting treatment within two months of symptom onset was 47%; this increased to 77% within four months. Delays of more than four months were more common among older patients, the UK born, and those of white or Pakistani ethnicity. According to the revised outcome categories, 2 in 2014, 87% of rifampicin sensitive patients without CNS, spinal, miliary or cryptic disseminated disease completed treatment within 12 months, consistent with recent years. The most common reason for not completing treatment was being still on treatment (5%). Completion was lower among those who were older, white or had at least one social risk factor. Among those with CNS, spinal, miliary or cryptic disseminated TB, 54% had completed treatment within 12 months. This increased to two thirds (66%) by last recorded outcome, with 21% still on treatment. Overall, 3% of rifampicin sensitive cases notified in 2014 died before completing treatment. The median age at death was 67 years, but TB caused/contributed to the death of five individuals under the age of 40. A further 4% were lost to follow-up, two thirds of whom had left the UK. Loss to follow up was much more common among the non-uk born, and slightly more common among those with at least one social risk factor. Isoniazid (6.8%) and multi-drug (1.1%) resistance decreased slightly in Patients of mixed/other ethnicities had the highest levels of resistance to at least one first-line drug. In 2015, the proportion of drug resistance among UK born and non-uk born individuals was similar. Levels of resistance among UK born cases, however, have substantially decreased since Although resistance was more than twice as common among those with a previous history of TB, they accounted for only a small proportion of resistant cases (10%). There were 15 cases of multi-drug resistant TB in 2015, of whom three were extensively drug resistant. All were born in different countries, including one in the UK. Among 7

8 patients with rifampicin resistant disease, notified in 2013, 65% completed treatment at 24 months; a fifth remained on treatment, 12% were lost to follow-up and one had died. An increasing proportion of TB patients in London had a social risk factor, commonly multiple factors (11% of those aged 15 years or older in 2015). Since 2011, there has been a steady increase in the proportion of cases among the homeless, as well as among drug users. Social risk factors were more than twice as common among those born in the UK than those born abroad. Individuals with social risk factors were more likely to have infectious and drug resistant forms of TB, and were more often hospitalised (especially those who were homeless). In conclusion, recent trends show sustained reductions in TB case numbers in London. These reductions were predominantly among those born abroad, which has halved since the peak in 2005, with most of the decrease since This is likely to be due in part to the implementation of pre-entry screening, but will also be affected by changes in migration patterns (particularly decreasing numbers of migrants from high TB burden countries), as well as a reflection of decreasing rates of TB worldwide. Small but sustained decreases in TB incidence were also seen among the UK born population, although this remains double the England average. This, in addition to a decrease in the rate of TB in UK born children under 15 years of age, and reduction in the proportion of cases that cluster with at least one other London case, suggests a reduction in TB transmission in London, as seen elsewhere in England. This is likely a reflection of improvements in TB control, including initiatives to tackle TB in under-served populations, which until recently had minimal measurable impact in this population. As cases become more concentrated in under-served populations, services will need to sustain and adapt their efforts to continue to tackle TB in the capital. Recommendations London TB control board should prioritise and work with wider stakeholders to develop strategies to improve outcomes for under-served populations. Continued support by NHS, PHE and allied services of cohort review as the tool to quality assure TB case and contact management according to national guidance. 9 Issues and themes identified at cohort reviews across London to be reported to the London TB Control Board in a systematic way. Close monitoring of multi-drug resistant TB between NHS and PHE, including the use of BTS MDR advisory service and MDR-specific TB cohort reviews. 8

9 Locally driven reviews of delays, outcomes and contact tracing as well as deaths should be carried out, with support and review by the London Clinical Leadership Group and London TB Control Board. PHE to monitor the implementation of LTBI testing and treatment and use local epidemiology to inform future developments. 9

10 1. TB notifications and incidence Overall numbers, rates and geographical distribution In 2015, 2,269 cases of tuberculosis (TB) were notified among London residents; a rate of 26 per 100,000 population (Figure 1). As seen across England, 1 the TB rate in London continued to decline, with a 12% decrease from the rate observed in 2014 and an overall reduction of 39% since London still has the highest rate in the country, accounting for 39% of the 5,758 cases in England. 1 Figure 1: TB case notifications and rate, London, (TB Monitoring Indicator 1) As in previous years, the highest TB notification rate was reported among residents of north west London, at 35 per 100,000 population. This was, however, a 24% decrease from the rate observed in 2014, and continued further a decrease since 2011 (Figure 2). Rates and numbers fell slightly in north east north central, and south east London, but increased slightly in south west London. 10

11 Figure 2: TB case rate by health protection team area of residence, London, Historically, there has been little change with regards to which local authority residents have the highest rates of TB (Figure 3). In 2015, Newham (250 cases, 75 per 100,000) and Brent (165 cases, 51 per 1000) had the highest TB notification rate, followed by Ealing (159 cases, 46 per 100,000), Hounslow (114 cases, 42 per 100,000) and Redbridge (114 cases, 38 per 100,000). All other local authorities had less than a hundred cases. Rates in Hounslow and Ealing, however, decreased by approximately 25% compared with Rates similarly fell in Brent and Redbridge (by 20% and 13% respectively), while those in Newham showed little change. Overall, rates fell most markedly among residents of Kensington and Chelsea (down 42% from 2014). Figure 3: TB case rate by upper tier local authority of residence, London, 2015 Enfield Hillingdon Harrow Barnet Waltham Forest Haringey Redbridge Havering Brent Hackney Camden Islington Barking and Dagenham Newham Ealing Westminster Tower Hamlets Kensington and Chelsea City of London Hammersmith and Fulham Greenwich Hounslow Southwark Lambeth Bexley Wandsworth Richmond upon Thames Lewisham Merton Kingston upon Thames Sutton Croydon Bromley TB rate per 100,000 population <

12 At smaller geographical resolutions there existed a high degree of variation in TB incidence, such that high overall rates could often be attributed to a relatively small number of very-high incidence middle super output areas (Figure 4). This was the case for Newham, Brent, Ealing, Hounslow and Redbridge. Figure 4: TB case rate by Middle Super Output Area of residence, London, 2015 Demographic characteristics Age and sex In 2015, 60% (1,361) of TB cases were male. Consistent with recent years, rates were also higher among males (32 per 100,000) than females (21 per 100,000), with an average of 13 additional cases per 100,000 among males over the past five years. The TB notification rate was highest among adults aged years, irrespective of gender (Figure 5). 12

13 Figure 5: TB case reports and rate by age and sex, London, 2015 Although there remained a distinction between children, adolescents and adults, rates did not appreciably differ across the age-strata of adults. This converging trend had been observed since 2013, and was largely due to falling rates among those years of age (Figure 6). Figure 6: TB case rate by age group, London,

14 In 2015, 101 cases of TB were reported in children under the age of 16, of whom 69% (70) were born in the UK. Similar to recent years, 33 cases occurred in children aged less than five years (5 per 100,000), 85% (28) of whom were UK born. Of these, most were of black African (36%, 10/28) or mixed/other ethnicity (29%, 8/28), consistent with recent years. Place of birth and time since entry Similar to previous years, 81% (1,838/2,266) of cases notified in 2015 were among individuals born outside of the UK, a higher proportion than seen across England (where 73% were born outside the UK). 1 Although, at 58 per 100,000 population, the TB notification rate for those born abroad was over seven times higher than for the UK born population (8 per 100,000), this was a 13% decrease from 2014, and half the rate reported for this population in 2005 (112 per 100,000). The TB notification rate among the UK born population similarly decreased by 12% relative to 2014, as did the number of cases (428 in 2015). Rates among the UK born in London had remained at around 10 per 100,000 between 2002 and 2012, before steadily decreasing to 7.9 per 100,000 in While the rate among the non-uk born in London was only slightly higher than the England average (51 per 100,000), the rate in the UK born in London remains more than twice the national average (of 3.4 per 100,000). 1 Figure 7: TB case notifications and rate by place of birth, London, (TB Monitoring Indicator 2) 14

15 In 2015, information on the time between entry to the UK and notification of TB was available for 96% (1,760/1,838) of non-uk born cases. The overall reduction in non-uk born cases was initially due to a reduction in very recent entrants (diagnosed less than two years after entry): this reduced by half between 2011 and 2013 (594 to 272), with smaller reductions since 2013 to 199 cases in The reduction in non-uk born cases between 2013 and 2015 was driven by a 42% reduction in the number of cases occurring among individuals who had been in the UK for 2-5 years (718 in 2013 to 416 in 2015). At this time there was also a smaller reduction in cases who had been in the UK 6-10 years (467 in 2013 to 360 in 2015). Cases among those who have been in the UK for 11 or more years increased slightly. Figure 8: Time between entry to the UK and TB notification for non-uk born cases by year, London, In 2015, country of birth was known for 1,784 (97%) of those born abroad. As in previous years, the highest proportion of cases occurred among those born in India (26%, 465 cases). This represented an 18% decrease in the number born in India relative to 2014, and a 39% reduction relative to The majority of this decrease occurred among those years of age (267 in 2015 vs. 487 in 2013), in particular among those who had arrived 2-5 years earlier (131 in 2015 vs. 257 in 2013). After India, the most common countries of birth were Pakistan, Bangladesh, Somalia, Nigeria and Nepal (Table 1). Together, individuals from these countries comprised 56% (1,025/1,838) of non-uk born TB cases, and 45% of all TB cases in London. This compares with the most common countries of birth in the non-uk born general 15

16 population of London, which in 2015 were India, Poland, Pakistan, Bangladesh, Nigeria and the Republic of Ireland. 3 Table 1: Ten most common countries of birth of non-uk born TB cases, London, 2015 Country of birth n % of non-uk born patients median years since entry India Pakistan Bangladesh Somalia Nigeria Nepal Romania Philippines Afghanistan Sri Lanka Ethnicity Rates fell or remained stable across all ethnic groups in 2015 compared with 2014 (Figure 9). As seen in recent years, London residents of Indian ethnicity experienced the highest rate of TB (98 notifications per 100,000 population), and accounted for the largest proportion of cases overall (25%, 574/2,263). This was, however, a 19% reduction from the rate observed in 2014, and a 40% reduction from Since 2012, those of Indian ethnicity have experienced a year-on-year decrease in the incidence of TB, and this marked the first time in over a decade that the notification rate fell below 100 per 100,000 population. Although the second highest rate was among those of Pakistani ethnicity (89 per 100,000 population), these accounted for only 10% of cases overall (226). The next highest rate was among those of black African ethnicity (73 per 100,000 population), which was also the second most common ethnic group (21%, 476). This rate, however, represented a 14% decrease from 2014, and continued further an overall decrease since In 2015, rates among the white, black other and black Caribbean populations were among the lowest in London, accounting for 14% (311), 2% (43) and 4% (89) of cases respectively. At least two fifths of cases in each of these ethnic groups were born in the UK (45%, 40% and 63% respectively); markedly higher than for other ethnic groups. 16

17 Figure 9: TB case rate by ethnic group, London, Ethnicity among UK-born cases The ethnicity distribution among UK-born cases (Figure 10) is notably different from that of the London TB case population overall: cases were more often among those of white (33%, 140/427) or black African ethnicity (17%, 73). This was also different from the UK born case population of England, 1 where 60% were white, and only 13% total were from black ethnic groups (black Caribbean, black African and black other). Figure 10: Proportion of UK-born TB cases by ethnic group, London,

18 Occupation In 2015, occupation information was complete for 92% (1,962) of the 2,128 cases aged 18 years or older (Table 2). Of these, 185 (9%) cases occurred in those working or engaged in education, almost all students (85%, 157). Most of these students were born outside of the UK (76%, 119). Of the 783 cases among people not currently working, half were unemployed (389) and another 31% (243) were retired. Table 2: Occupational category of persons with TB aged 18 years and older, London, 2015 Occupation n % Education Student Health care worker Other None Retired Unemployed Total Clinical characteristics Site of disease In 2015, nearly half of all TB patients had pulmonary disease (Table 3). As seen in recent years, the second most common site was extra-thoracic lymph node TB, accounting for a quarter of cases. 18

19 Table 3: Site of disease of TB patients, London, 2015 Site of Disease n % Pulmonary Lymph Nodes (extra thoracic) Lymph Nodes (intra thoracic) Pleural Other Gastrointestinal/Peritoneal Bone/Joint (spine) CNS (meningitis) (Bone/Join (other - not spine) Miliary CNS (Other - not meningitis) Genitourinary Cryptic Disseminated Laryngeal *patients may have disease at more than one site, so the total % will not equal 100% Pulmonary TB was more common among UK-born patients (62%, 267/428) than those born abroad (45%, 826/1,838). As in recent years, pulmonary TB was more common among those of white (75%, 232/311) and Chinese ethnicity (61%, 14/23), and less common among those of Bangladeshi (33%, 45/138), Indian (38%, 216/574) and Pakistani ethnicity (38%, 87/226). Previous history of tuberculosis In 2015, 6.3% (142/2,240) of cases had been previously diagnosed with TB. This was consistent with recent years. 2. Laboratory confirmation of TB Laboratory tests data collection Data for all culture confirmed TB isolates from the Mycobacterium Reference Laboratories, including speciation, drug susceptibility testing and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR) typing were matched to TB case notifications and the results were used to report culture confirmation. Results for microscopy, PCR and histology were also collected in ETS. 19

20 Culture confirmation and speciation As in previous years, 59% (1,339) of cases were culture confirmed in This was higher among those with pulmonary TB (74%, 809/1,095 vs. 45%, 530/1,174 of patients with exclusively extra-pulmonary TB). Of those cases that were culture confirmed, the vast majority were Mycobacterium tuberculosis (98%, 1,308), with only three cases of M. bovis, and 25 cases of M. africanum. Three cases could not be categorized beyond belonging to the M. tuberculosis complex. Sputum smear In 2015, sputum-smear results were known for 78% (850/1,095) of patients with pulmonary TB. Of these, 45% (386) were smear-positive, consistent with recent years. 3. TB transmission It is not currently possible to directly measure TB transmission at a population level, so proxy measures are required. The rate of TB in children is widely accepted to be a good indicator of TB transmission in a community. Molecular genotyping of the organisms causing TB in a population can also provide insight into putative transmission chains. Rate of TB in UK born children In 2015, the rate of TB in UK born children under 15 years of age in London an indirect indicator of recent transmission was estimated at 4.4 per 100,000 population (95% CI , 86 cases). This represents a reduction in this rate since 2008 (Figure 11), when rates were at their relative highest (9.2 per 100,000 population, 204 cases). Small numbers of cases among children, however, mean year on year changes should be interpreted with caution. 20

21 Figure 11: Rate of TB in UK born children under 15 years of age, London, (TB Monitoring Indicator 5) Strain typing and clustering The National TB Typing service in England was established in 2010 and since that time all TB isolates have been typed using 24 loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR). Such strain typing identifies clusters of cases with indistinguishable strains that may be due to recent transmission. 4 While these clustered cases may reflect cases that are part of the same chain of recent transmission, this could also reflect common endemic strains circulating either within England or abroad. Thus the detection of a common strain type among cases does not confirm recent transmission. Additional epidemiological information is required to assess whether a common strain type is likely to reflect recent transmission. MIRU- VNTR strain typing can be used to refute transmission between individuals who have different strain types. Proportion of cases clustered and geographical distribution In 2015, 99.7% (1,335/1,339) of culture confirmed cases in London residents had an isolate that was strain typed and 93% (1,244) had at least 23 loci typed (Table 4). Overall, between 2010 and 2015, 87% of isolates were typed with at least 23 loci and 52% were identified as belonging to 1,108 London clusters. Although the remaining 48% (4,561/9,406) had a unique strain in London, 722 (8%) were clustered with another 21

22 case outside of London, bringing the total number of national clusters that included at least one London case to 1,758. The proportion of cases that clustered with at least one other case in London declined from the peak of 55% in 2012 to 47% in 2015, as did the number of new clusters that formed each year, which fell from 250 in 2012 to 110 in Among the cases in London clusters in 2015, 77% (453/589) clustered with at least one other patient in 2015 or 2014, in 199 clusters. Of these 199 clusters 15 had MDR cases, 39 had a child under 15 years of age and 104 had cases with one or more social risk factors. Table 4: Number and proportion of clustered cases and new clusters by place of birth and year, London, Year Culture confirmed cases ,950 1, ,089 1, ,092 1, , ,773 1, ,540 1, ,339 1, Total 10,783 9, , , , ,108 a % 23 loci is the proportion of culture confirmed cases who have had at least 23 loci typed b Clustered in time period ( ), clustered cases notified per year c A new cluster forms at the point when a second London case is notified with an indistinguishable MIRU-VNTR strain type as an existing case in London Size of clusters >23 loci typed Cases in Cases in cluster: Non-UK born Cases in cluster: UK born Of the 1108 clusters from , the median cluster size was three cases (range 2-118). The majority of clusters (79%; 875/1,108) were small in size (<5 cases), with 49% (548) containing only two cases (Figure 12). Twenty eight London clusters composed 20 or more cases (range ): these comprised 22% (1,079/4,845) of all clustered cases in London. New clusters cases a clusters b (per year) c n n % n % n % n % n 22

23 Figure 12: Proportion of clusters by size, London, Cluster lineage The most common lineage of London clusters was the Euro American lineage, which accounted for 43% (472) of clusters observed between 2010 and 2015 (Table 5). Clusters of Central Asian lineage comprised 26% (284), followed by East African Indian (15%, 170) and Beijing (5%, 53). The distribution of cluster size in London tended to be similar across lineages (median cluster size 2-3). However, 17% (9/53) of Beijing lineage clusters contained ten or more cases compared with less than 8% of others. This may reflect that the 24 loci MIRU-VNTR strain typing used in England is less discriminatory in this lineage. Table 5: Cluster lineage and size, London Cluster Number of East African Euro American Central Asian size clusters Indian Beijing Other* n n % n % n % n % n % Total 1, *includes cases with M.bovis, M.africanum, multiple lineages and cases where no lineage has been identified Whole genome sequencing Whole genome sequencing (WGS) of M. tuberculosis complex isolates provides information on Single Nucleotide Polymorphism (SNP) differences between isolates. This provides more information than the currently deployed method (MIRU-VNTR strain typing) on how isolates are related to each other. 23

24 PHE is close to deploying the use of WGS for TB throughout England. This new technology will add to our understanding of TB transmission by providing robust genomic information to be used in conjunction with epidemiological and surveillance information. 4. Delay from onset of symptoms to start of treatment Time from symptom onset to treatment start for patients with pulmonary TB Information on time from symptom onset to treatment start was available for 93% (1,013/1,095) of pulmonary TB cases in 2015 (Table 6). Eleven patients were asymptomatic at diagnosis. The median time symptomatic was 64 days, with an interquartile range (IQR) of days. This was five days less than the median delay for London cases in 2014 and eight days less than the median for England in Table 6: Time between symptom onset and treatment start in pulmonary TB cases*, London, (TB Monitoring Indicators 6 and 7) 0-2 months 2-4 months >4 months Total Year n % n % n % n *excluding those with missing onset or treatment start dates Characteristics of pulmonary TB cases with a delay from onset of symptoms to treatment of more than four months Comparable proportions of males and females had a greater than four month delay between symptom onset and treatment (23%, 145/640 vs. 25%, 93/373). The proportion of pulmonary TB cases who experienced delays of more than four months increased with age, from 12.5% (5/40) in children under the age of 15, to 33% (43/130) in adults over the age of 64. It was slightly more common for UK born cases to wait in excess of four months compared with non-uk born cases (29%, 69/241 vs. 22%, 169/770). Overall, the highest proportion of cases with a delay of more than four months to treatment occurred in those of white (30%, 64/211) and Pakistani ethnicity (28%, 23/81). Although a high proportion of Chinese cases also waited in excess of four months (31%, 4/13), numbers in this group were small, and should be interpreted with caution. 24

25 5. TB outcome in drug sensitive cohort Drug sensitive cohort For the purposes of TB outcome reporting the drug sensitive cohort excludes all TB cases with rifampicin resistant TB (initial or amplified) including MDR-TB (initial or amplified), and non-culture confirmed cases treated as MDR-TB. 2 Under this definition, cases with resistance to isoniazid, ethambutol and/or pyrazinamide but without resistance to rifampicin are included in the drug sensitive cohort. For TB outcomes in the drug resistant cohort, see Chapter 6. Treatment outcomes for the drug sensitive cohort are reported separately for the following groups: for cases with an expected duration of treatment less than 12 months, TB outcomes at 12 months are reported. This group excludes cases with CNS disease, who have an expected duration of treatment of 12 months. In addition, those with spinal, miliary or cryptic disseminated disease are excluded from this group, as CNS involvement cannot be reliably ruled out for the purposes of reporting for cases with CNS, spinal, miliary or cryptic disseminated disease, the last recorded treatment outcome is reported. For cases notified in 2014, however, information on final outcome was collected in 2015 so may be only one year after start for many patients In 2014, 2,552 cases of TB were notified, of which 2,529 (99%) were sensitive to rifampicin and therefore included in the drug sensitive cohort. 1: Outcomes for TB patients with expected duration of treatment less than 12 months (cases notified in 2014) Similar to previous years, 88% (2,233) of those notified with rifampicin-sensitive TB in 2014 did not have CNS, spinal, military or cryptic disseminated disease. Among these, the majority (87%, 1,946/2,232) completed treatment within 12 months, consistent with recent years (Table 7). 25

26 Table 7: Number and proportion completing treatment at 12 months, London, * TB patients n % Total *excludes rifampicin resistant TB, and patients with CNS, spinal, miliary or cryptic disseminated disease At 12 months, 5.4% (120) of cases were still on treatment, making this the most common reason for not having completed treatment within 12 months (Table 8). Of these, 53% (64) were on a planned treatment regimen that exceeded 12 months (31% of these due to initial isoniazid resistance), 32% (38) had their treatment regimen changed (equally attributable to intolerance, poor clinical response and initial/amplified drug resistance) and 15% (18) had their treatment interrupted. Table 8: TB outcome at 12 months, London, cases diagnosed in 2014* Outcome at 12 months n % Completed 1, Died Lost to follow up Still on treatment Treatment stopped Not evaluated Total 2,232 *excludes rifampicin resistant TB, and patients with CNS, spinal, miliary or cryptic disseminated disease As seen in recent years, treatment completion was slightly higher among females (89%, 778/878) than males (86%, 1,168/1,354). Treatment completion also decreased with age: 94% (102/108) of children under 15 years of age completed treatment within 12 months vs. 78% (175/224) of adults over the age of 65. A slightly higher proportion of UK born cases (89%, 388/435) completed treatment within 12 months as compared with non-uk born cases (87%, 1,557/1,795). 26

27 Treatment completion was lowest among individuals of white ethnicity (82%, 236/288), regardless of whether or not they were UK born (Figure 13). Social risk factors were reported by 36% (16/45) of white individuals who did not complete treatment, higher than for other ethnic groups. Overall, treatment completion was worse among those with at least one social risk factor (81%, 164/202) compared to those without any risk factors (89%, 1,695/1,915). Figure 13: Treatment completion within 12 months by place of birth and ethnic group, London, cases notified in : Outcomes for drug sensitive cohort of patients with CNS, spinal, miliary or cryptic disseminated TB (cases notified in 2014) Of the 296 cases of CNS, spinal, miliary or cryptic disseminated disease notified in 2014, 54% (161) completed treatment within 12 months. This increased to 66% (196) by the last recorded outcome (Table 9). Among the 194 cases for whom duration of treatment was known, the median treatment time was days (IQR ); approximately one year. A fifth of cases (21%, 61) were still on treatment at the last recorded outcome, and two (0.7%) had their treatment stopped. 27

28 Table 9: Overall outcome for patients with rifampicin sensitive CNS, spinal, miliary or cryptic disseminated disease, London, cases diagnosed in 2014* Overall outcome n % Completed Died Lost to follow up Still on treatment Treatment stopped Total 296 *excludes rifampicin resistant TB Demographic trends in treatment completion at 12 months were similar to those reported for rifampicin sensitive TB patients without CNS, spinal, miliary or cryptic disseminated disease. A higher proportion of females completed treatment at 12 months as compared to males (58%, 61/106 vs. 53%, 100/190). Older patients were again less likely to complete: just 38% (12/32) of those aged 65 or older completed within 12 months compared to 56% (149/264) of those aged less than 65. Similar proportions of UK born (54%, 22/41) and non-uk born (55%, 139/254) individuals had completed treatment at 12 months, and treatment completion was slightly less common among those with at least one social risk factor (52%, 13/25 vs. 57%, 143/252 among those without risk factors). Deaths and lost to follow up in the drug sensitive cohort (at 12 months since diagnosis) Overall, 3% (75/2,528) of rifampicin sensitive cases notified in 2014 died within 12 months of starting treatment. TB reportedly caused or contributed to over half of these deaths (59%, 44), was incidental to 20 (27%), and had an unknown relationship to the remaining 11 (15%). Three cases were diagnosed at post-mortem, with TB listed as the cause of death for one. The median age at death was 67 years (IQR 54-79), but TB caused or contributed to the death of five individuals under the age of 40 (all of whom were non-uk born, and including one aged just 13 years old). Death was slightly more common among UK born (3.8%, 18/476) than among those born abroad (2.7%, 56/2,049). Similar to previous years, 4% (101/2,528) of rifampicin sensitive cases notified in 2014 were lost to follow-up at 12 months. Of these, two thirds (66%, 65/99) had left the UK. All but three of the cases lost to follow up were known to have been born abroad, such that the proportion lost among non-uk born cases was over seven times higher than among UK born cases (4.7%, 97/2,049 vs. 0.6%, 3/476). A slightly higher proportion of males were lost to follow-up (4.5%, 69/1,544 vs. 3.3%, 32/984 of females), as were those with at least one social risk factor (4.8%, 11/227 vs. 3.6, 79/2,167 of those without). The median age of cases lost to follow up was 31 (IQR 26-41). 28

29 6. Drug resistant TB (including outcomes in the drug resistant cohort) Drug resistance Overall initial drug resistance and geographical distribution In 2015, resistance profiles were available for all but ten of the 1,339 culture confirmed cases. The proportion of culture-confirmed TB cases resistant to one or more first line drug decreased slightly to 7.3% (97/1,329) relative to 2014 (8.2%, 126/1,534). Over the past 16 years, the proportion with first-line resistance has remained between 7 and 11% (Figure 14). The decrease since 2013 was seen in both the proportion resistant to isoniazid (from 8.3%, 146/1,755 to 6.8%, 91/1,329) and multi-drug resistant (MDR, from 2.2, 38/1,755 to 1.1%, 15/1,329). Small numbers, however, mean year on year changes should be interpreted with caution. Figure 14: Proportion of TB cases with initial first line drug resistance, London, In 2015 similar proportions of males (7.2%, 61/842) and females (7.4%, 36/487) with TB were resistant to at least one first-line drug. The proportion of drug resistant cases was highest among those aged 20 to 49 years, (8.3%; 75/901) compared to 5.9% (20/341) 29

30 among those aged 50 years and older and 2.3% (2/87) among those aged less than 20 years. While in 2015, the proportion of drug resistance among UK born (6.7%, 15/224) and non-uk born (7.4%, 82/1,103) cases were similar, there has been a substantial decrease in the proportion resistant among UK born cases (from 14% in 2011 (42/293), mainly a result of the decline in isoniazid resistance). In 2015, TB patients of mixed/other ethnicities (including black other) had the highest levels of resistance (11%, 27/251): both among the UK and non-uk born. The most common countries of birth of patients with drug resistant TB of mixed/other ethnic groups were the Philippines (6/26) and Nepal (4/26). The most common countries of birth, however, of all drug resistant cases in 2015 were the United Kingdom (15/94) and India (14/94). Among those born in the UK, the proportion of cases with resistance to at least one first line drug was similar for black Caribbean (9.7%, 3/31), white (8.6%, 7/81), and Pakistani (7.7%, 1/13) ethnic groups, though numbers in each were very small. Drug resistance was slightly higher among those with pulmonary TB (7.9%, 63/801) than those with exclusively extra-pulmonary disease (6.4%, 34/528). Similar to 2014, 9.6% (35/365) of sputum smear positive cases had drug resistant TB. Drug resistance was more than twice as common among cases with a previous history of TB (15%, 10/67) compared to those without (6.9%, 86/1,246). However, these accounted for only 10% (10/96) of resistant cases. Second line drug resistance and extensively drug resistant (XDR) TB In 2015, 15 (1.1%, 15/1329) cases were MDR, three of whom met criteria for extensively drug resistant (XDR) TB. All fifteen were born in different countries, including one from the UK. The most frequent world region of birth was sub-saharan Africa (5/15), although this represented only 1.9% of cases born in this region. Five were black African, five were of mixed/other ethnicity (including black other), three were white, one Indian and one Bangladeshi. Only two patients with MDR disease had a previous history of TB, both of whom were born abroad. 30

31 TB outcome at 24 months for patients with rifampicin resistant disease (cases notified in 2013) In 2013, 43 TB cases were rifampicin resistant at start of treatment and no additional cases were reported as becoming rifampicin resistant while on treatment. Five individuals were previously treated for TB (12%), and 40 (93%) were born abroad. Thirty-eight individuals (88% of rifampicin resistant cases) had MDR TB initially, two of whom had XDR TB. There were no reports of rifampicin resistant cases becoming MDR while on treatment. Four were lost to follow-up within 12 months (all born abroad and three known to have left the UK). At 24 months, 28 had completed treatment, nine were still on treatment, one had died and another one lost to follow up (Table 10). Table 10: TB outcome at 24 months for patients with rifampicin resistant disease, London, cases diagnosed in 2013 Outcome at 24 months n % Completed Died Lost to follow up Still on treatment Total TB in under-served populations Social risk factors In this section, social risk factors are presented for TB cases aged 15 years and older, and are defined as current or history of homelessness, drug use and imprisonment, or current alcohol misuse. In 2015, 11% (230/2,098) of London cases aged 15 years and older had one or more social risk factor (Table 11). This was a small increase from 2014, and was consistent with a nationally increasing trend. 1 Drug use was the most common risk factor (4.5%, 96/2,135), followed by homelessness (4.3%, 91/2,127), alcohol misuse (4.1%, 87/2,111) and imprisonment (2.5%, 53/2,125). Since 2011 there has been a steady increase in the proportion of cases among the homeless, as well as among drug users. As seen in recent years, among individuals with at least one social risk factor, nearly a third had multiple issues (31%, 72/230). 31

32 Table 11: Social risk factors among TB patients, London, Year n % Total Social risk factors were more than twice as common among those born in the UK (20%, 71/353 vs. 9% 158/1,744 among non-uk born). Among the 158 non-uk born cases with at least one social risk factor, a disproportionate number were either black African (32%, 51 vs. 22%, 397/1,813 of all adult non-uk born cases) or white (19%, 30 vs. 9%, 169/1,813). Among UK born cases with at least one social risk factor, whites were similarly over-represented (49%, 35/71 vs. 38%, 136/362 adult UK born cases), as were those of black Caribbean ethnicity (27%, 19/71 vs. 14%, 50/362). Those with at least one social risk factor were more than twice as likely to be infectious than those with none (38%, 88/230 had sputum smear positive pulmonary TB vs. 15%, 279/1,868 among those without social risk factors). Although individuals with social risk factors represented just 11% of cases, they accounted for one in four (88/367) infectious cases. In 2015, over a fifth of cases aged 15 years and older who were resistant to at least one first-line drug had one or more social risk factors (22%, 20/92). Drug resistance was also nearly twice as common among those with at least one social risk factor (12.3%, 20/163 vs. 6.6%, 72/1,096 among those without any risk factors). As seen nationally, 1 cases with at least one social risk factor had more often been previously diagnosed with TB (13.3%, 30/225 vs. 5.7%, 106/1,858 among those without any risk factors). Deprivation Since 2010, when the Index of Multiple Deprivation was first introduced, the distribution of cases by London deprivation quintile has remained stable. Over half of TB patients notified in 2015 lived in areas that constituted the two most deprived quintiles of London (57%, 1,304/2,269), compared with 7% (151) in the least deprived quintile. Rates similarly correlated with deprivation, and were more than four times higher in the most deprived areas compared to the least (Figure 15). 32

33 Figure 15: TB case rate by deprivation, London, HIV testing & TB-HIV coinfection, hospitalisation, directly observed therapy and BCG HIV testing In 2015, information on HIV testing was available for 99.6% (2,165/2,174) of cases with previously unknown HIV status. Of these, 97.3% (2,107) were offered and received testing; above the national figure of 93.5%. 1 Another 1.4% (31) of cases were offered but did not receive testing, of whom a quarter declined (26%, 8). In London, the proportion of cases not offered a test was 1.2% (27), as compared to 3.8% (191/5,016) nationally. TB-HIV co-infection The latest available information on TB-HIV co-infection for notified adults 15 years and above, estimated that 3.4% (96) of London TB cases in 2013 were co-infected with HIV. 5 This continues a decline in the number and proportion co-infected since 8.8% (257) of cases in 2003 were estimated to be co-infected. 33

34 Hospital inpatient and directly observed therapy As seen in previous years, nearly a third (32%, 721/2,259) of cases notified in 2015 had been a hospital inpatient at some point throughout treatment. The proportion hospitalised increased with age, such that 48% (129/270) of those 65 years or older had been inpatients. Hospitalisation was also more common among those with at least one social risk factor (53%, 120/228), particularly if they had a history of homelessness (64%, 58/91). Consistent with recent years, over half of initially MDR cases were hospitalised at some point in care (53%, 8/15) Since 2009, the proportion of cases who received directly observed therapy (DOT) has steadily increased, with 17% (376/2,268) of cases in 2015 reportedly on DOT. A higher proportion of children under the age of 15 (31%, 27/86) and adults 65 years or older (27%, 72/271) received DOT. Among those with one or more social risk factor, 56% (128/230) were placed on DOT, compared with only 12% (226/1,950) of those without any social risk factors. Almost half of initially MDR cases received DOT (47%, 7/15) BCG vaccination Information on BCG vaccination was available for 1,812 (80%) of London cases notified in 2015, of whom 76% (1,384) were vaccinated (Table 12). Among cases less than 15 years of age, the proportion vaccinated increased to 83% (62/75). This compares to 70% (133/190) of TB cases aged 0-14 in England overall. As seen in recent years comparable proportions of UK born and non-uk born cases had been vaccinated. Estimated BCG vaccination coverage in the nine boroughs with TB rates of over 40 per 100,000 and universal BCG policy in London ranged from 32% in Brent to 91% in Newham. 1 Please refer to the national report for BCG vaccine coverage data: B_annual_report_2016.pdf Table 12: Number and proportion of TB patients with BCG vaccination, London, 2015 <5 years old <15 years old All ages n(n) % n(n) % n(n) % UK born 21(25) (55) (361) 73.4 Non-UK born 3(5) (20) (1451) 77.1 All cases 24(30) (75) (1812)