TB in children: treatment and prevention in England, 2021
Updated 3 August 2023
Applies to England
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About this report
Report series
The aim of this report is to describe the tuberculosis (TB) treatment pathways, outcomes and prevention in children in England up to the end of 2021. It is the seventh in a series of 7 reports which have previously been published as a single report titled TB in England. This is the first year that they have been published as a series of smaller reports and each will describe different aspects of TB incidence, treatment, and prevention in England.
Related reports
- TB incidence and epidemiology in England, 2021
- TB diagnosis, microbiology and drug resistance in England, 2021
- TB in children: Incidence, epidemiology and microbiology in England, 2021
- TB treatment in England, 2021
- TB treatment outcomes in England, 2021
- TB prevention in England, 2021
- TB in children: Treatment and prevention in England, 2021
Report format
Information on how this series of reports fits within the TB Action Plan for England 2021 to 2026 (jointly published with NHS England) along with a list of key monitoring indicators for the report series can be found in TB incidence and epidemiology in England, 2021.
Intended audience
This report is primarily aimed at healthcare professionals involved in the management of people with TB, healthcare commissioners involved in the planning and financing of TB services, public health professionals, researchers, and governmental and non-governmental organisations involved in TB control.
Main messages
This report covers TB treatment and outcomes in children (under 15 years old), plus data on use of the Bacillus Calmette-Guérin (BCG) vaccine to prevent severe TB in children.
The epidemiology, incidence and microbiology of TB in children in 2021 is reported in the TB in children: incidence, epidemiology and microbiology in England, 2022 report.
In 2021:
- TB was reported in 129 children, a decrease of 13% compared to 2020 when 149 children were notified
- directly observed treatment (DOT), a treatment adherence strategy where the patient takes treatment under direct in-person observation by a designated individual, was offered to one in 4 children with TB, of whom 82% were recorded as having received it
- almost two-thirds of children notified with TB were assessed as requiring enhanced case management (ECM), a package of tailored supportive care in addition to standard management but which guidelines state should be offered to all children with TB
- TB diagnostic delay (time from onset of symptoms to TB diagnosis) accounts for most of TB treatment delay (time from onset of symptoms to start of treatment) with median diagnostic delay of 36.5 days
- TB treatment was initiated at a median of 5.5 days after TB diagnosis and overall treatment delay is unchanged when compared with the previous 6 years
- children were less likely to experience treatment delay when compared to other age groups, with approximately half the risk of a treatment delay over 2 months compared with those aged 15 to 44 years old (risk ratio 0.57, 95% CI 0.37 to 0.88)
- only 52.2% of notifications of children with TB were notified within the 3-day window from diagnosis, as set out in the Health Protection Regulations, which is comparable to previous years but slightly less than for adults (57.4%)
- the proportion of children with non-severe TB that are not multi-drug resistant (MDR) or rifampicin resistant (RR) TB (non-MDR or non-RR TB) who successfully completed TB treatment remained stable at around 90%
- coverage for the 5 local authorities who have conducted universal BCG vaccination programmes ranged from 43.3% to 66.7% in the financial year 2021 to 2022, compared with 20.6% to 79.2% in the previous financial year
Directly observed treatment (DOT)
According to NICE guidelines, DOT should be offered as part of enhanced case management (ECM) to children who themselves or whose parents:
- do not adhere to treatment (or have not in the past)
- have been treated previously for TB
- have a history of homelessness, drug or alcohol misuse
- are currently in prison, or have been in the past 5 years
- have a major psychiatric, memory or cognitive disorder
- are in denial of the TB diagnosis
- have multidrug resistant TB
- request DOT after discussion with the clinical team
- are too ill to administer the treatment themselves
Data reporting on whether DOT was offered and received by children with TB from 2011 is shown in Table 1 of the TB in children: Treatment and prevention in England data set.
In 2021, missing data in relation to the offer of DOT was the lowest since 2011 at 39.5%.
In 2021, DOT was offered to 26.4% (34 out of 129) of all children notified with TB. When limited to the 78 for whom information was recorded, this increased to 43.6% (34 out of 78). 82.4% (28 out of 34) who were offered DOT received it. DOT was offered but not recorded as received in 5 cases.
A greater proportion of children were offered DOT when compared with adults (15 years and over) and limited to those with information recorded (43.6% vs 27.4%) (TB treatment in England, 2021 report and Table 2 of the TB treatment in England, 2021 data set).
Enhanced support for children undergoing TB treatment
ECM is a package of tailored supportive care comprising 3 levels, plus standard management. All children notified with TB should be offered at least level one of ECM. The ECM levels recorded in the national TB surveillance system (NTBS) comprise of:
- level 0 for standard care management
- level 1 for people with clinical or social issues or both which have an impact on treatment, which may include children with TB, or those with HIV and taking antiretrovirals
- level 2 for people with complex clinical or social issues or both affecting treatment and necessitating, for example, weekly visits and may include persons with complex side effects or single drug resistance
- level 3 for people with very complex clinical or social issues or both affecting treatment and necessitating DOT or video enhanced therapy (VOT) and may include people experiencing homelessness, multidrug resistant (MDR) or rifampicin-resistant (RR) TB, or those with complex contact tracing or cases in which the involvement of social services is required (see the Royal College of Nursing’s Case Management Tool for TB Prevention, Care and Control in the UK)
Table 1 shows levels of ECM by year. In 2021, almost two-thirds of all children notified with TB (61.2%) were assessed as requiring some level of enhanced case management. This is comparable with 2020, but a higher proportion than in 2018 and 2019, mainly due to an increased number of children being assessed as needing ECM level 1.
Table 2 of the TB in children: Treatment and prevention in England data set shows the proportion of children by age, sex, place of birth and site of disease who were assessed as requiring different levels of ECM in 2021. ECM was most frequently assessed as being required for non-UK-born children and for those in the 0 to 4 years age group.
Table 1. Enhanced case management (ECM) among children notified with TB by year, England, 2018 to 2021
| Year | Total | Any ECM | Level 1 | Level 2 | Level 3 | Unknown level |
|---|---|---|---|---|---|---|
| 2018 | 147 | 77 (52.4%) | 8 (5.4%) | 0 (0.0%) | 53 (36.1%) | 16 (10.9%) |
| 2019 | 169 | 83 (49.1%) | 9 (5.3%) | 3 (1.8%) | 42 (24.9%) | 29 (17.2%) |
| 2020 | 149 | 92 (61.7%) | 24 (16.1%) | 3 (2.0%) | 41 (27.5%) | 24 (16.1%) |
| 2021 | 129 | 79 (61.2%) | 30 (23.3%) | 5 (3.9%) | 32 (24.8%) | 12 (9.3%) |
Delays in the patient pathway among children
The prompt diagnosis and treatment of active TB can improve treatment outcomes and reduce the period of infectiousness and potential onwards transmission.
Breakdown of the period of treatment delay into the periods between symptom onset, seeking healthcare, diagnosis and then start of treatment can identify where further research into the causes of delay and of appropriate interventions should be targeted.
The TB treatment in England, 2021 report provides an overview of delays in the patient pathway for all people with TB.
Time from symptom onset to TB treatment start (treatment delay)
Treatment delays for children with pulmonary TB
For the 2021 data set, information was analysed on the time between symptom onset to treatment start for 60.0% (42 out of 70) of children notified with pulmonary TB. Children excluded from the analysis included those that were missing data for date of symptom onset (19), missing dates of both treatment start and symptom onset (6) or did not yet start treatment (3). Reasons for missing date of symptom onset can include when children are identified as asymptomatic cases during contact tracing of adult cases.
Table 2 shows the proportion of children notified with pulmonary TB with a treatment delay between 2 to 4 months and more than 4 months from 2016 to 2021. Over this period there was no notable change in the proportions that experienced treatment delays. Compared to previous years, a higher proportion of cases was missing information on treatment delays in 2021 (40%), which was mainly due to an increase in missing information for date of symptom onset.
In 2021, two-thirds (28 of 42 cases, 66.7%) of children with pulmonary disease were treated within 2 months from TB symptom onset. Seven (16.7%) children experienced a delay of more than 4 months from symptom onset to treatment start (Table 2).
Compared with all people with TB, children were approximately half as likely to experience treatment delays of 2 to 4 months or over 4 months (TB treatment in England, 2021 report).
Table 2. Number and proportion of children with treatment delay notified with pulmonary TB, England, 2016 to 2021
| Year | 2 to 4 months delay | Over 4 months delay | Total (n) | Missing (%) | Total pulmonary (n) |
|---|---|---|---|---|---|
| 2016 | 21 (18.4%) | 11 (9.6%) | 114 | 24 (17.4%) | 138 |
| 2017 | 15 (15.2%) | 19 (19.2%) | 99 | 10 (9.2%) | 109 |
| 2018 | 23 (25.3%) | 13 (14.3%) | 91 | 17 (15.7%) | 108 |
| 2019 | 14 (17.3%) | 10 (12.3%) | 81 | 29 (26.4%) | 110 |
| 2020 | 16 (19.8%) | 7 (8.6%) | 81 | 15 (15.6%) | 96 |
| 2021 | 7 (16.7%) | 7 (16.7%) | 42 | 28 (40.0%) | 70 |
Notes:
- 2 to 4 months covers 61 to 121 days and over 4 months includes delays from 122 to 730 days. Delays over 730 days are excluded.
- Children diagnosed with TB post-mortem are excluded from these analyses.
- The total includes the number of children with pulmonary TB with known duration of treatment delay.
- The total pulmonary reflects the number of children with pulmonary TB, including those with no known duration of treatment delay.
In 2021 the median treatment delay for children notified with pulmonary TB was 42 days (IQR: 15 to 77 days) compared with 23 days in 2020 (the lowest recorded treatment delay since 2011, but with no consistent change between 2011 to 2020). The median treatment delay of 42 days is the highest recorded between 2011 and 2021 (Table 3 of the TB in children: Treatment and prevention in England data set). In adults, the median treatment delay in 2021 was 79 days (IQR: 40 to 153 days), the joint highest since 2011 (with 2017 also having a delay of 79 days) (Table 7 of the TB treatment in England, 2021 data set).
Time from symptom onset to TB diagnosis in children (diagnostic delay)
In 2021, information was analysed on the time between symptom onset to date of diagnosis for 62.9% (44 out of 70) of children with pulmonary TB. The 26 children not included were all missing a date of symptom onset. The median diagnostic delay was 36.5 days between symptom onset and TB diagnosis, compared with 23 days in 2020, which was the lowest recorded since 2011 as shown in Table 3 of the TB in children: treatment and prevention in England data set.
In 2021, the median treatment delay was 5.5 days longer than diagnostic delay compared with 2020 when median treatment and diagnostic delays were equivalent at 23 days. The difference between diagnostic and treatment delay was greater in 2021 compared with previous years, with the longest difference between diagnostic and treatment delay previously at 4 days in 2013 and 3 days in 2019 (note that the average over all years excluding 2021 is 1.3 days).
Breakdown of treatment delay in children notified with pulmonary disease
Figure 1 shows breakdowns of treatment delay for years with sufficient data available (2017 to 2021). The proportion of treatment delay due to the time between symptom onset and presentation at a health facility has varied over the last 5 years, at:
- 28% in 2017
- 48% in 2018
- 56% in 2019
- 43% in 2020
- 36% in 2021
This suggests that a larger proportion of the delay to treatment start is healthcare-related delay in diagnosis of the child with TB (Figure 1). This contrasts with all people with TB where a greater proportion of treatment delay was consistently accounted for by patient-related delay as measured by the interval from symptom onset to healthcare presentation (TB treatment in England, 2021).
Figure 1. Breakdown of median treatment delay among children with pulmonary TB, by time from symptom onset to presentation at any healthcare service and time from presentation at healthcare service to start of treatment, England, 2017 to 2021
Notes:
- This figure is limited to children with a known duration of treatment delay and a valid date for first presentation at healthcare service, on or before the start of treatment. The number of children included out of those with known treatment duration was 70 out of 99 (78%) in 2017, 86 out of 91 (95%) in 2018, 78 out of 81 (96%) in 2019, 77 out of 81 (95%) in 2020 and 42 out of 42 (100%) in 2021.
- The date of presentation to any healthcare service refers to the earliest date the child was seen by healthcare professionals, whether this was at a health facility or at a TB service.
Numbers are too low to provide an overview of TB treatment delays among children by geographical subregions other than at the national level. Treatment delays by UKHSA centre and upper-tier local authority districts for all people with TB are available in the TB Treatment in England, 2021 report and Tables 8 and 9 of the TB treatment in England, 2021 data set.
Treatment delay by age group, sex and place of birth
Due to small numbers, the following data are presented as aggregated numbers across the last 5 years. Table 3 shows the proportion of children notified with pulmonary TB between 2017 to 2021 who experienced treatment delay by age group and Table 4 shows the same by sex and Table 5 by place of birth. In the last 5 years, the majority of children (66.8%) started treatment within 2 months of symptom onset compared with 39.4% of pulmonary TB cases for all people notified with TB (Table 5 of the TB treatment in England, 2021 data set). A treatment delay of more than 2 or 4 months was more common in older age group children compared with children aged less than 5 years (Table 3). Treatment delay was also more common in male than female children, with 67.8% of boys experiencing a treatment delay compared with 34.1% of girls (Table 4). It was also more common in children born outside of the UK (40.0%) compared with UK-born children (30.3%, 88 out of 290) (Table 5). These differences were not seen when assessed in all people notified with TB (Table 10 of the TB treatment in England, 2021 data set).
Children were less likely to experience a treatment delay compared with all other age groups, with approximately half the risk of a treatment delay over 2 months compared with people with pulmonary TB aged 15 to 44 years old (risk ratio 0.57, 95% CI 0.37 to 0.88) (TB Treatment in England, 2021 report and Table 11 of the TB Treatment in England, 2021 data set).
Data for treatment delay by age group and sex for children in 2021 is presented in Table 4 of the TB in children: treatment and prevention in England data set.
Table 3. Average number and proportion of children with treatment delay notified with pulmonary TB by age group, England, 2017 to 2021
| Time from symptom onset to treatment start | 0 to 4 years | 5 to 9 years | 10 to 14 years | Total |
|---|---|---|---|---|
| 0 to 2 months | 125 (75.3%) | 55 (67.9%) | 83 (56.5%) | 263 (66.8%) |
| 2 to 4 months | 24 (14.5%) | 14 (17.3%) | 37 (25.2%) | 75 (19.0%) |
| Over 4 months | 17 (10.2%) | 12 (14.8%) | 27 (18.4%) | 56 (14.2%) |
| Total | 166 | 81 | 147 | 394 |
Notes:
- The row and column totals include the number of eligible children notified with pulmonary TB with a valid duration between symptom onset and treatment start.
- ‘0 to 2 months’ covers 0 to 60 days, ‘2 to 4 months’ covers 61 to 121 days and ‘over 4 months’ includes delays from 122 to 730 days.
Table 4. Average number and proportion of children with treatment delay notified with pulmonary TB by age group and sex, England, 2017 to 2021
| Age group (years) | Female | Male | Total (n) |
|---|---|---|---|
| 0 to 4 | 20 (24.7%) | 64 (75.3%) | 84 |
| 5 to 9 | 10 (27.8%) | 29 (64.4%) | 39 |
| 10 to 14 | 44 (44.0%) | 27 (57.4%) | 71 |
| Total | 74 (34.1%) | 120 (67.8%) | 194 |
Notes:
- The row and column totals include the number of eligible children notified with pulmonary TB with a valid duration between symptom onset and treatment start between 60 and 730 days.
Table 5. Average number and proportion of children with treatment delay notified with pulmonary TB by place of birth, England, 2017 to 2021
| Time from symptom onset to treatment start | Non-UK-born | UK-born | Total (n) |
|---|---|---|---|
| 0 to 2 months | 60 (60.0%) | 202 (69.7%) | 262 (67.2%) |
| 2 to 4 months | 21 (21.0%) | 52 (17.9%) | 73 (18.7%) |
| Over 4 months | 19 (19.0%) | 36 (12.4%) | 55 (14.1%) |
| Total | 100 | 290 | 390 |
Notes:
- The row and column totals include the number of eligible children notified with pulmonary TB with a valid duration between symptom onset and treatment start and a known place of birth.
- ‘0 to 2 months’ covers 0 to 60 days, ‘2 to 4 months’ covers 61 to 121 days and ‘over 4 months’ includes delays from 122 to 730 days.
Delays in notification
Notification of TB is required within 3 days of a suspected or confirmed TB diagnosis. The median reporting delay for children with pulmonary TB in England has fluctuated around 3 to 5 days from 2016 to 2021 (Table 3 of the TB in children: treatment and prevention in England data set). Data was excluded for those with post-mortem diagnosis and those with a delay over 90 days (1 child in 2021, 58 children from 2011 to 2021).
In 2021, just over half of children with TB (52.2%) were notified within 3 days of diagnosis, which is slightly less compared with the proportion of all people with TB notified within 3 days (57.2%) (Table 12 of the TB treatment in England, 2021 data set). However, it is the highest proportion since 2015 (Table 5 of the TB in children: treatment and prevention in England data set).
TB treatment outcomes in children with non-MDR or non-RR TB
Treatment outcomes at 12 months and last recorded treatment outcome
Treatment outcomes are reported according to the year of notification. For children treated for non-MDR or non-RR TB, outcomes are reported for those notified up to and including 2020 as that is the latest year of notifications for whom treatment completion is expected within the 2021 data. For children treated for MDR or RR TB, outcomes are reported for those notified up to and including 2019. For further definitions of TB treatment cohorts please see the Methodology and definitions section.
Mutually exclusive treatment outcome categories are shown in Table 6 below. For 142 children with non-MDR or non-RR TB notified in 2020 with non-severe disease, 125 (88%) had completed treatment by 12 months and 1 child (0.7%) had died. Half of the 8 children notified in 2020 and reported to still be on treatment at 12 months subsequently completed treatment at their last recorded outcome, increasing overall treatment completion to 90.8% (Table 6). At the time of data extraction, 4 were still reported to be on treatment and none had stopped treatment or were lost to follow up. All of the 8 children notified in 2020 and reported as not evaluated at 12 months remained as non-evaluated at the last recorded outcome. Treatment outcomes for children over time (2011 to 2021) at 12 months are shown in Table 6 of the TB in children: Treatment and prevention in England data set and last recorded treatment outcome over the same time period in Table 7 of the TB in children: Treatment and prevention in England data set.
Table 6. TB outcome at 12 months and the last recorded TB outcome for children with non-MDR or RR TB, with an expected treatment duration of less than 12 months, England, 2020
| Treatment outcome | Treatment outcome at 12 months (%) | Last recorded treatment outcome (%) |
|---|---|---|
| Treatment completed | 125 (88.0%) | 129 (90.8%) |
| Died | 1 (0.7%) | 1 (0.7%) |
| Lost to follow-up | No observations | No observations |
| Still on treatment | 8 (5.6%) | 4 (2.8%) |
| Stopped | No observations | No observations |
| Not evaluated | 8 (5.6%) | 8 (5.6%) |
| Total | 142 | 142 |
Notes:
- Excludes children with MDR or RR TB and those with miliary or cryptic disseminated TB or TB meningitis.
- ‘Not evaluated’ includes unknown and transferred out.
The action plan target for all people notified with TB is to increase treatment completion within 12 months to 90% by 2026 for those with non-severe disease and an expected treatment duration of less than 12 months. Figure 2 below shows this target is met for children in all years except the most recent year of analysis. Treatment completion for children has remained stable over the last 10 years, ranging from 88.0% in 2020 to 96.3% in 2012 (Table 6 of the TB in children: Treatment and prevention in England data set). Similar to other years, treatment completion at 12 months is greater in children compared with all people with TB, which ranged from 84.2% for notifications in 2020 to 87.8% for notifications in 2012 over the last 10 years (Table 1 of the TB treatment outcomes in England data set). The apparent lower proportion of treatment completion in the most recent analytical year (2020 notification year) is likely to increase as data continues to be updated and may not represent a true large decrease (see previous TB annual reports.
Figure 2. Proportion of children treated for non-MDR or non-RR TB with expected treatment duration less than 12 months who completed treatment within 12 months
Figure 3a and Figure 3b show treatment outcomes at 12 months for children with non-severe and non-MDR or RR TB expected to complete treatment within 12 months over time. The proportion of those not evaluated for the 2020 cohort is expected to decrease as more missing values are entered over time. The proportion of children who died, were lost to follow up, still on treatment or stopped treatment has remained very low and comparable from 2011 to 2021 (Figure 3b). From 2011 to 2020, 2 deaths were reported, of which 1 was incidental to TB (13 years old child) and the other had an unknown relationship to TB diagnosis (less than 1 year old child). Deaths among the entire non-MDR or non-RR TB cohort (all people notified with TB) are discussed in the TB treatment in England, 2021 report.
Figure 3a. Treatment outcome at 12 months for children with non-MDR or non-RR TB with expected treatment duration less than 12 months, England, 2011 to 2020
Figure 3b. Breakdown of children evaluated who did not complete treatment at 12 months for children with non-MDR or non-RR TB and expected treatment duration less than 12 months, England, 2011 to 2020
12-month treatment outcomes by age and sex
Treatment outcomes at 12 months for the cohort of children treated for non-MDR or non-RR TB and without severe disease are reported in the following tables of the TB in children: Treatment and prevention in England data set:
- by age group from 2011 to 2020 in Table 8 of the data set
- by age and sex for notifications in 2020 in Table 9 of the data set
Treatment completion in children aged 0 to 4 years was over 90% in all years, except for 2011 (89.2%). In those aged 5 to 9 years, treatment completion ranged from 80.5% to 97.8% (with the lowest proportion in 2021) while it ranged from 87.2% to 96.4% in those aged 10 to 14 years old. There were no clear trends in either direction over time (Table 8 of TB in children: Treatment and prevention in England data set).
Among children with TB notified in 2020, treatment completion was similar between males and females at 90.3% and 87.7% respectively. When assessed within age sub-groups treatment completion in children aged 5 to 9 years old was 64.7% in 17 girls compared with 91.7% in 24 boys. This difference is most likely the result of chance from small numbers in these sub-groups. In the 0 to 4 and 10 to 14 years age groups females were slightly more likely to complete treatment at 12 months compared with males (Table 9 of TB in children: Treatment and prevention in England, 2021 data set). The proportion of male children completing treatment decreases slightly as age increases (92.0% in 0 to 4 year olds, 91.7% in 5 to 9 year olds and 87.0% in 10 to 14 year olds). There was no evidence of differences in treatment completion by age or sex when aggregated across the last 5 years (Table 10 of TB in children: Treatment and prevention in England, data set).
Please see the section Factors affecting treatment completion at last recorded outcome in the entire non-MDR or non-RR cohort for quantification of the associations of demographic factors with treatment completion as the last recorded outcome for children notified with TB between 2016 and 2020.
Numbers are too low to provide an overview of TB treatment outcomes among children by geographical subregions other than at the national level. Treatment outcomes by UKHSA centre for all people with TB are available in the TB treatment outcomes in England, 2021 report and Tables 5 and 11 of the TB treatment outcomes in England, 2021 data set.
Treatment duration
Of 142 children notified in 2020 who were expected to complete treatment within 12 months, 128 (90.1%) had a recorded treatment end date. Of these, most completed treatment within the standard 6 to 8 months (77.3%, 99 out of 128). Just over 6% completed in less than 6 months, shorter than the full duration of the standard course, which may occur if a child started treatment abroad. Since 2011, the proportion of children who take longer to compete their treatment from 8 to 10 or 10 to 12 months has remained consistent at around 7% and 4% (Table 11 of the TB in children: Treatment and prevention in England, 2021 data set).
TB treatment outcomes for the non-MDR or non-RR TB cohort with severe disease
Table 12 of the TB in children: Treatment and prevention in England, 2021 data set shows last recorded treatment outcomes for children notified with severe TB (TB meningitis, miliary or cryptic disseminated TB) by year from 2011 to 2020. From the 5 children notified in 2020 with TB meningitis and without MDR or RR TB, 4 completed treatment at the last recorded outcome and 1 child under 1 year old had died, where TB was recorded as causal for the death.
Last recorded TB treatment outcomes for the entire non-MDR or non-RR TB cohort
Last recorded treatment outcome for the entire non-MDR or non-RR TB cohort, including those with miliary or cryptic disseminated TB or TB meningitis are shown in the TB in children: Treatment and prevention in England, 2021 data set:
- by year (2011 to 2020) in Table 13
- by site of disease (2020) in Table 14
Treatment completion as the last recorded outcome for the entire non-MDR or non-RR TB cohort has not notably changed over time, with a peak of 98.9% in 2014 and a 10-year average of 96.7%. This is higher than among the entire non-MDR or RR-TB cohort including all age groups, where the 10-year average treatment completion was 88.9% (Table 9 of the TB treatment outcomes in England, 2021 data set).
Factors affecting treatment completion at last recorded outcome in the entire non-MDR or non-RR cohort
As shown in Table 10 of the TB in children: Treatment and prevention in England, 2021 data set, when aggregated over the last 5 years there were only small differences in the proportion of children who completed TB treatment by the socio-demographic and disease characteristics of age, sex, place of birth, pulmonary disease and treatment delay. The 95% confidence intervals of the risk ratios all crossed 1, suggesting that observed differences in treatment completion occurred by chance.
TB treatment outcomes in the drug resistant (MDR or RR TB) cohort
Table 15 of the TB in children: Treatment and prevention in England, 2021 data set shows TB treatment outcomes at 24 months for children notified with MDR or RR TB by year from 2010 to 2019 and totalling 27 children The 2019 cohort comprised 1 child treated for MDR or RR TB, who completed treatment within 12 to 18 months.
Table 16 of the TB in children: Treatment and prevention in England, 2021 data set shows the last recorded treatment outcome for the same group, of whom 25 completed treatment at last recorded outcome, and 1 child notified in 2015 was reported as still on treatment as the last recorded outcome.
TB prevention in children
BCG vaccination
The BCG vaccination programme has undergone several changes in response to changing trends in TB epidemiology plus the recent change to programme delivery.
The BCG immunisation programme is a risk-based programme recommended for individuals at higher risk of exposure to TB. This includes all infants (0 to 12 months) with a parent or grandparent who was born in a country where the annual incidence of TB is over 40 TB cases per 100,000 population per year. In addition to this, all infants living in an area of the UK with an incidence above 40 per 100,000 population should be offered the BCG vaccine.
Detailed information on the BCG programme can be found in the Green Book. Please note an update to this chapter is due in 2023. Evaluation studies have identified that BCG is most effective against the most severe forms of the disease, such as TB meningitis in children and less effective in preventing respiratory disease, which is the more common form in adults.
The timing of the neonatal BCG immunisation was changed to a 28-day immunisation programme in September 2021. This change was prompted by the evaluation of the addition of screening for severe combined immunodeficiency (SCID) to the routine new-born screening test at 5 days of age. As the attenuated BCG vaccine is contraindicated in babies with positive SCID screen, sufficient time is needed to allow the outcome of the SCID screening to be available before proceeding with BCG vaccination, therefore making BCG immunisation at 28 days necessary to avoid potential risk of adverse effect of BCG on severely immunocompromised babies. You can read more about this in the BCG immunisation programme: changes from September 2021 letter.
Since April 2015, as part of the Cover of Vaccination Evaluated Rapidly (COVER) programme, BCG has been included in the childhood vaccine coverage data extraction from local child health information systems (CHIS). However, for local authorities conducting selective BCG immunisation, data on the number of eligible children based on risk assessment is not available for the period reported here.
In Table 7, BCG vaccine coverage data is presented for the 5 local authorities in London that have offered universal vaccination, and for the first time, coverage of the selective programme for Leicester local authority, the only local authority for which incidence has recently come very close to the 40 per 100,000 per year threshold.
Of the 5 authorities who have offered universal vaccination only Newham still had a TB incidence greater than the 40 per 100,000 population per year by 2022.
Table 7. Annual BCG vaccine coverage of children up to 1 year old in English local authorities with universal BCG programmes and Leicester local authority: April 2021 to March 2022
| Upper tier Local Authority | Three-year average (2017 to 2019) annual TB rate per 100,000 | Number of eligible children 2021 to 2022 | Universal BCG coverage in 2021 to 2022 (%) | Universal BCG coverage in 2020 to 2021 (%) |
|---|---|---|---|---|
| Newham | 45.0 (41.0 to 49.2) | 5,515 | 66.7 | 79.2 |
| Brent | 37.6 (33.9 to 41.6) | 4,346 | 36.7 | 30.0 |
| Hounslow | 31.2 (27.5 to 35.3) | 3,534 | 44.9 | 20.6 |
| Ealing | 37.5 (33.9 to 41.4) | 4,495 | 43.3 | 40.6 |
| Redbridge | 31.2 (27.7 to 35.0) | 4,344 | 63.2 | 74.6 |
| Leicester | 39.7 (36.0 to 43.7) | 4,452 | 54.2 | 51.8 |
Notes:
- Data on BCG vaccine coverage presented in this table is obtained from NHS Digital’s Childhood Vaccination Statistics, 2021 to 2022 and Childhood Vaccination Statistics 2020 to 2021.
- Vaccination cohorts run per financial year, the time period 2021 to 2022 refers to children born between 1 April 2020 and 31 March 2021.
- The BCG vaccination programme was based on the 2012 to 2014 local authority TB rates, as published in the TB England Annual report.
Coverage for the local authorities who have conducted universal BCG vaccination programmes ranged from 43.3% to 66.7% in the financial year 2021 to 2022, compared with 20.6% to 79.2% in the previous financial year (Table 7). Leicester, which conducted selective vaccination, achieved higher coverage of all children compared with Brent, Hounslow and Ealing, all of whom conducted universal vaccination, despite all 3 of these local authorities increasing their coverage in the current year compared to the previous.
Full data on the number of children up to 12 months who received BCG in all other the remaining local authorities are available from NHS Digital’s Childhood Vaccination Statistics 2021 to 2022.
Figure 4a. Three-year average rates of TB in English local authorities with universal BCG programmes and Leicester over time, England, 2014 to 2021
Notes:
- BCG vaccine coverage data was obtained from the NHS Digital Childhood Vaccination Statistics from 2016 to 2021.
- The year relates to the 3-year average rate of TB from that year and the 2 years prior.
Figure 4b. Annual BCG vaccine coverage of children up to 1 year old in English local authorities with universal BCG programmes and Leicester
Notes:
- BCG vaccine coverage data was obtained from the NHS Digital Childhood Vaccination Statistics from 2016 to 2021.
- Vaccination cohorts run per financial year, the time period 2021 to 2022 refers to children born between 1 April 2020 and 31 March 2021.
Areas with high TB incidence were selected for universal BCG coverage due to the increased risk of transmission of TB from infected adults to infants in these areas. Figure 4a and Figure 4b show 3-year average rates of TB for the local authorities in England who have conducted universal BCG vaccination programmes plus Leicester and annual BCG vaccination coverage in these areas. Newham has consistently had the highest 3-year moving average TB notification rate, but this has decreased from 69.0 per 100,000 in 2014 to 2015 to 41.4 per 100,000 by 2019 to 2021 matched by the highest BCG coverage. Redbridge had an increase in BCG coverage from approximately 30% in the financial year 2016 to 2017 to near 80% between 2019 to 2020. Until recent years Brent has had some of the highest TB incidence but also some of the lowest BCG coverage rates. Hounslow reported a large decrease in coverage across the main pandemic period of 2020 to early 2021. Leicester has experienced a slow rise in TB incidence in recent years, while reporting a stable rate of BCG coverage.
Discussion and conclusions
Treatment delays continue to be an issue in the diagnosis and management of TB in children, but these delays are lower for children then for all other age groups with TB. One third of children diagnosed with TB were delayed by 2 months or more, and half of these experienced a delay of at least 4 months. Analysis presented here indicates the greatest delay is healthcare-related delay in time to diagnosis from first presentation at a healthcare service rather than patient-related delay. Reasons for this are likely to be multifactorial and include the time point when TB is first considered as a diagnosis and the challenges associated in obtaining clinical samples in children. TB in children can present with limited symptoms and those that are present can be features of other illness such as fever or weight loss. Treatment completion in children remained stable and high at 90% indicating successful treatment outcomes for children with TB.
Due to the duration of treatment, and support to parents, families and children, the British Association for Paediatric TB suggests that all children require ECM 1 or 2 as a minimum. From the data presented here, two-thirds of children with TB were identified as needing ECM. This was more frequently observed for younger children and those who were non-UK born. From the data presented here, 18% of children recommended for additional support through DOT are recorded as not having received it, but the reasons for this are not known. From this report there is an indication that there is a potential gap in the provision of ECM and DOT for children with TB.
Vaccination with BCG vaccine in at-risk infants remains an important prevention measure in TB control in England. The BCG programme in England remains a selective at-risk programme with the exception of 5 local authority areas who offer a universal programme. The TB Action Plan has set objectives in relation to the BCG with a target of 80% of those eligible receiving an offer of BCG vaccination. This data is routinely collected as part of COVER. Further assessment is being undertaken by UKHSA in partnership with the Health Protection Research Unit for Vaccines, co-hosted by the London School of Hygiene and Tropical Medicine, through a service evaluation of the change to the BCG programme, implemented in September 2021, after the introduction of the SCID screening pilot
From the data provided for this report, even in areas where universal coverage is recommended, the recorded uptake varied between 43.3% to 66.7% in the financial year 2021 to 2022 indicating that the overall target of 80% has not been reached. Within this there may be issues with data completeness.
Recommendations
These recommendations are linked to the corresponding priorities in the TB action plan for England, 2021 to 2026.
Recommendation 1
Further analysis of the issues relating to diagnostic delay in children should be undertaken. The TB Action Plan has specific objectives in relation to understanding the factors leading to diagnostic delay. This analysis should include a review of the time taken for a child to be clinically assessed by a paediatrician and discussed with a named TB Consultant as outlined in the British Association for Paediatric TB Clinical Guidance Care of children and young people exposed to or infected with TB.
Recommendation 2
Factors affecting the ability to assess and offer both ECM and DOT should be further explored by TB services caring for children with TB. Where gaps in potential service provision for children with TB, these should be reviewed with the commissioners of the service and as part of the Getting it Right First Time review of TB.
Recommendation 3
UKHSA should continue to be actively involved in the ongoing evaluation of the BCG programme following the changes in the programme delivery in relation to SCID screening.
Methodology and definitions
General methodology for TB notifications, data production, cleaning and reporting are described in the methodology and definitions section of TB incidence and epidemiology in England, 2021.
BCG data
Since April 2015, as part of the Cover of Vaccination Evaluated Rapidly (COVER) programme, BCG has been included in the childhood vaccine coverage data extraction from local CHIS. However, for local authorities conducting selective BCG immunisation, data on the number of eligible children based on risk assessment is not routinely available. For this reason, BCG coverage data is presented only for areas offering a universal BCG programme.
In 2020 to 2021, a universal BCG programme was offered by 5 local authorities (LAs), all of which were in London (Newham, Brent, Hounslow, Ealing and Redbridge). A coverage figure is reported for these LAs running a universal programme as well as Leicester which runs a selective programme but has an average annual rate of TB over 40 per 100,000 (considered high TB incidence). Data on the number of children up to 12 months who received BCG in the remaining LAs are available in the COVER report available. Full data on the number of children up to 12 months who received BCG in all of the other remaining local authorities are available from NHS Digital’s Childhood Vaccination Statistics, 2021 to 2022.
Enhanced Case Management (ECM)
Numbers and proportions of people with ECM per level, and those receiving DOT, were calculated for all of those with information on ECM and DOT available in UKHSAs surveillance systems (NTBS/enhanced TB surveillance (ETS)). People who had information on DOT/VOT but were missing ECM data, were coded as ‘Yes’ for any ECM and coded into level 3 of ECM. Those who had missing information on any ECM but were recorded as being in level 0 of ECM (equivalent to standard treatment) were recoded as having ‘No’ in the ECM binary variable of ECM required, thereby considerably reducing proportion of notification with missing information.
The percentage of any ECM was calculated as the proportion of cases that reported ‘Yes’ (1) to ECM, or (2) to DOT offered or (3) DOT received out of all cases with information. The percentage of ECM per level was calculated as the proportion of cases with a known level of ECM out of all cases with information on ‘any ECM required’ (‘Yes’ or ‘No’). The percentage missing data is calculated as the proportion of all TB notifications for each year with no information recorded in (1) ECM required, (2) ECM level required, (3) DOT offered, or (4) DOT received.
Diagnostic delays
Delays to TB diagnosis is calculated as the days difference between self-reported date of TB symptom onset and the date of TB diagnosis as recorded in UKHSAs surveillance systems (NTBS/ETS). Diagnostic delays are not calculated for those who were diagnosed with TB at post-mortem and those with missing data, so these are not included in the denominator for the proportion of people with delays to TB diagnosis. Diagnostic delays exceeding 2 years (730 days) are excluded from analysis as symptoms lasting for over 2 years are thought to relate to another episode of TB. Negative diagnostic delays, resulting from symptoms presenting post diagnosis, were also excluded from the analysis as these are likely to indicate data errors or treatment side effects as opposed to disease symptoms.
Reporting delays
Reporting delay is calculated as the days difference between TB diagnosis date and date of TB notification to UKHSAs surveillance systems (NTBS/ETS). Reporting delays are not calculated for those who were diagnosed with TB at post-mortem and those with missing data, so these are not included in the denominator for the proportion of people with reporting delays. Reporting delays exceeding 3 months (90 days) are excluded from analysis as these delays typically reflect changes outside of healthcare control (such as a patient moving abroad, not attending treatment, or having died) as opposed to true healthcare delays to notifying the case.
Treatment delays
Treatment delay is calculated as the days difference between self-reported date of TB symptom onset and the date treatment started as recorded in UKHSA’s surveillance systems (NTBS/ETS). Treatment delays are not calculated for those who have not started treatment, those who were diagnosed with TB at post-mortem and those with missing data, so these are not included in the denominator for the proportion of people with treatment delays.
Treatment delays exceeding 2 years (730 days) are excluded from analysis as symptoms lasting for over 2 years are thought to relate to another episode of TB. Negative treatment delays, resulting from symptoms presenting post treatment start, were also excluded from analysis as these are likely to indicate data errors or treatment side effects as opposed to disease symptoms. Where treatment delays are categorised, categories comprise of:
- 0 to 2 months (0 to 60 days)
- 2 to 4 months (61 to 121 days)
- more than 4 months (121 to 730 days)
Statistical methods
Confidence intervals
95% confidence intervals are model derived and were calculated using assumptions of the binomial distribution for proportions.
Comparisons of proportions
Chi-squared tests were used to compare proportions. P values less than 0.05 are reported as ‘statistically significant’.
Risk ratios
Risk ratios are model derived using the binomial distribution for proportions.
Software packages
All statistical analysis was carried out using Stata 17.0.
Glossary
Diagnostic delay
The diagnostic delay represents the time (in days) from when a person self-reported TB symptom onset to when they are diagnosed with TB.
Directly observed treatment (DOT)
DOT is a treatment strategy which refers to the patient taking treatment under direct in-person observation of a trained health care worker or designated individual to ensure treatment adherence for patients requiring ECM.
BCG vaccination
The BCG vaccine is primarily used against TB and has a protective effect against meningitis and disseminated TB in children but does not prevent primary infection nor the reactivation of latent pulmonary infection, limiting its impact on preventing TB transmission.
BCG immunisation programme
The BCG immunisation programme is a risk-based programme recommended for individuals at higher risk of exposure to TB. This includes infants (0 to 12 months) born to non-UK-born parents or UK-resident grandparents born in high TB incidence countries (more than 40 TB cases per 100,000 population per year). In addition to this, all infants living in an area with an incidence above 40 per 100,000 population should be offered the BCG vaccine. Detailed information on the BCG programme can be found in the Green Book. Please note an update to this chapter is due in 2023.
Enhanced case management
ECM is defined as the increased level of patient monitoring for people with (complex) clinical or social issues or both affecting treatment. There are 3 levels of ECM depending on the complexity of the clinical or social issue or issues or both and the intensity of patient monitoring required, ranging from fortnightly or weekly visits to necessitating DOT or VOT. ECM may be required for children with TB, those with HIV and taking antiretrovirals, people with complex side effects or single drug resistance and those with complex contact tracing or cases in which the involvement of social services is required. For more information see the nurse guidance document.
Post-mortem diagnosis
A person diagnosed at post-mortem is defined as having TB which was not suspected before death, but a TB diagnosis was made at post-mortem, with pathological and/or microbiological findings consistent with active TB that would have warranted anti-TB treatment if discovered before death.
Pulmonary TB
A person with pulmonary TB is defined as having TB involving the lungs and/or tracheobronchial tree, with or without extra-pulmonary TB diagnosis. In this report, in line with the WHO’s recommendation and international reporting definitions, miliary TB is classified as pulmonary TB due to the presence of lesions in the lungs, and laryngeal TB is also classified as pulmonary TB.
Risk ratios
Risk ratios quantify the relative risk of the outcome we are interested in between 2 different groups. For example, the relative risk of pulmonary disease in males compared with females. This is calculated as the proportion of males with pulmonary disease divided by the proportion of females with pulmonary disease, which is a risk ratio of 1.18 (95% CI 1.11 to 1.25). This is interpreted as males having an 18% increased risk of pulmonary disease compared with females and we have 95% confidence that the true increased risk lies within the range of 11% to 25%.
If a 95% CI for a risk ratio includes the value of 1.0 then we cannot infer that the true response ratio is different from 1. Thus, we would say that these results are not providing any evidence that the observed magnitude of the risk ratio is ‘statistically important’. If a risk ratio of less than 1.0 is reported, such as risk ratio 0.85, this is interpreted that the group of interest have a 15% reduced risk of the outcome.
The UK Health Security Agency (UKHSA)
The UKHSA was launched on October 1, 2021. It is an executive agency of the Department of Health and Social Care. The UKHSA is responsible for planning, preventing and responding to external health threats, and providing intellectual, scientific and operational leadership at national and local level as well as with partners in other countries. Most health protection functions are devolved to the other UK nations’ public health teams in the UK, so this report only covers TB notifications and data from England.
Treatment delay
Treatment delay represents the time (in days) from when a person self-reported TB symptom onset to when they start antibiotic treatment for TB.
Video observed therapy
VOT refers to the use of a videophone or other video or computer equipment by a patient to record their treatment intake whilst observed remotely by a trained health care worker or designated individual. This method is a flexible and non-invasive option to monitor treatment adherence in patients requiring ECM.
95% Confidence Interval
In this report, model-derived 95% confidence intervals (CI) are presented alongside relative risks. For example, the percentage of TB notifications with pulmonary disease is 52.7% (95% CI 51.3 to 54.2%). This can be loosely interpreted as that we have 95% confidence that the true but unknown value of this percentage in the population lies within the range of 51.3% to 54.2%.