Recent household transmission of tuberculosis in England, 2010–2012: retrospective national cohort study combining epidemiological and molecular strain typing data

Understanding whether tuberculosis (TB) cases are due to recent transmission or reactivation of remotely acquired latent infection would allow directed public health interventions to reduce TB. In England, a high proportion of TB cases are born abroad (73% in 2015), many of whom are likely to have been infected in their country of birth and reactivated in England [1].

Epidemiological information can help identify outbreaks. However, epidemiological data alone may either underestimate recent transmission (when there are no recognised epidemiological links) or overestimate recent transmission, especially in populations with an increased risk of TB, for example where there are a sizable number of persons who have immigrated from a high TB burden country, as evidenced by the utility of strain typing (ST) for refuting transmission [2].

Molecular ST data can provide information about whether cases are plausibly part of the same transmission chain. It can also be used to estimate the proportion of TB due to recent transmission, but has limitations [3]. ST data are only available for culture confirmed cases, and the currently used 24-loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTR) ST may not be discriminatory enough to adequately distinguish clusters [4]. ST data alone may overestimate recent transmission due to common strains circulating both in England and abroad [1]. Combining both epidemiological and ST data should provide better estimates of recent transmission.

Household contacts are at a higher risk of infection, and the household setting is an important reservoir for transmission [5, 6]. Studies have estimated the proportion of transmission within and outside the household in high-burden settings [3, 7‐10], but not in low-burden settings. Household contact screening is key for TB control; enabling identification of active and latent TB cases in the household, and prompt treatment initiation and prevention of further transmission. Additionally, ‘inform and advise’ information should lead to earlier diagnosis and treatment for subsequent cases. In the UK, guidance on close contact screening has recently changed. The British Thoracic Society guidance in 2000 advised screening household/close contacts of pulmonary cases [11]. The National Institute for Health and Care Excellence (NICE) guidance was revised in 2016, from screening all household contacts of active TB cases irrespective of the site of disease [12], to only screening household contacts of pulmonary TB cases [13].

Our aim was to combine epidemiological and ST data to estimate the proportion of TB due to recent transmission in households in England, describe the characteristics of those in whom transmission has occurred, and identify the factors associated with being a household transmitter. Additionally, we investigated the impact that identification of a household TB case had on time to diagnosis and treatment of subsequent cases.

TB cases notified to the Enhanced Tuberculosis Surveillance system in England between January 1, 2010, and December 31, 2012, were included in the analysis. All initial M. tuberculosis complex isolates were prospectively typed using 24-loci MIRU-VNTR ST, and data from isolates were probabilistically matched to TB case notifications [14].

To our knowledge, this is the first study to combine molecular ST and epidemiological data on links between cases to estimate the contribution of recent household transmission of TB at a national level. Our analysis of TB occurring over a 3-year period identified confirmed, probable and possible household transmission events, enabled us to describe diagnostic delay for index and subsequent cases in households, and allowed us to investigate risk factors for being a household transmitter.

We found that almost 8% of TB cases in England occurred within a household with another TB case, allowing us to estimate that 4% of TB cases were due to recent transmission within households. Given the lack of a gold standard for identifying recent transmission of TB, it is not possible to compare this to robust estimates of the overall proportion of TB cases attributable to TB transmission in England. In England, 58.4% of cases cluster by MIRU-VNTR, so the maximum proportion of cases that could be estimated to be due to recent transmission using this method is 47%, which would be an overestimate [1].

While only 30% of household index cases were born in the UK (similar to all notified TB cases) [1], we noted that 48% of subsequent household cases were UK-born (some likely to be children of non-UK-born parents). Whilst we might expect UK-born cases to be due to recent transmission in the UK, the fact that 10% of UK-born TB cases lived in a household with two or more cases suggests that earlier diagnosis and improved contact tracing could have an important impact in this group.

This study provides important insights into the characteristics of cases that transmit TB within households. After adjusting for age, sex and lineage, transmitters were more likely to be from Black-African, Indian and Pakistani ethnic groups in the UK-born, or from Somalia or Romania compared with India. Possible reasons these cases are more likely to transmit could include that they live in larger households, with different composition, socioeconomic status and overcrowding. The presence in the household of long-term visitors from high incidence countries, lack of awareness about TB, stigma resulting in obstacles to access healthcare/treatment, and lack of willingness to disclose information about contacts could also play a part. There is evidence that stigma, fear of discrimination, social exclusion and deportation, and other sociocultural factors can be barriers to Somali patients accessing TB services and disclosing their TB status to facilitate contact tracing [17‐20], but less research has been performed on obstacles faced by other communities. Interestingly, we found that UK-born cases of South Asian ethnicity were more likely to be household transmitters compared to those born in South Asia. One possible explanation is that both patients and clinicians may be less likely to suspect TB in UK-born cases compared to migrants, resulting in a longer diagnostic delay, increased periods of infectivity and more transmission. It would be interesting to explore the reasons for this differential level of transmission based on ethnicity and country of birth in future studies.

The majority of index cases were adults (86%) and almost 40% of subsequent cases were children. Surprisingly, given that children are usually considered to be less infectious than adults [21], we found children to be the index case in 14% of households. In the risk factor analysis, children had the highest odds of being a transmitter compared to other age groups, when comparing household transmitters with all other TB cases. This may in part reflect the fact that children always live in a household with other people, whereas adults may live alone, and when household transmitters were compared with all other household cases only, the odds of being a transmitter was lowest for children compared to 25–44 year olds. In some instances, all household cases could have been infected outside the household, but the child developed symptoms faster. However, as child transmitters were more likely to be smear and culture positive (and thereby have the potential to transmit) compared to non-transmitters, we should not assume that adults within the household are always the source case. Exposure to infectious TB may have occurred within the community, with the age of the child influencing both their risk of exposure [22] and the likelihood of transmitting to others.

There is significant delay from symptom onset to treatment start in pulmonary TB cases, with median delay of 72 days in 2015 [1]. We found that treatment delay was similar for index cases and subsequent household cases already symptomatic at the time of identification of the index. Household contact tracing should lead to earlier detection of incident active TB cases in the household. It is therefore of concern that there was a median delay of 29 days from the identification of the index case until subsequent symptomatic cases started treatment. For subsequent household cases who were asymptomatic when the household index case was identified, there was a reduction in the delay from symptom onset to treatment, likely due to contact tracing and to the provision of ‘inform and advise’ information. However, a median delay of more than 1 month (37 days) demonstrates there is potential to further reduce this delay.

Our study has many strengths; we used national data, ST results for all culture confirmed cases and complete data on addresses of cases over a 3-year period. However, there are limitations too; we have assumed that, if two cases occur in the same household and have indistinguishable MIRU-VNTRs, this represents recent household transmission. It may occasionally reflect transmission from a non-household source case to members of the same household, which may have occurred during a visit or in another setting. This study only collected data on active TB cases occurring within a household within a 3-year time period; we were not able to collect data on latent TB infection. We recognise that due to the long and variable incubation period for reactivation, this study may therefore underestimate household transmission. A high proportion of TB cases in the UK are not culture confirmed, and therefore do not have ST results. Household cases with ‘refuted’ transmission according to ST may be misclassified with differences occurring due to microevolution or technical limitations with the laboratory processes. Furthermore, some dates recorded in the surveillance system for symptom onset and first contact with healthcare may not be accurate and result in misclassification of household order.

Our study has a number of implications for household contact tracing in England. The fact that 25% of TB cases in households with ST results had discordant strains shows that households with multiple TB cases do not necessarily represent household transmission. ST data should be used to identify refuted cases of household transmission, and to inform the need for source contact tracing outside the household, especially for children. It is interesting to note that one-quarter of index cases in households had extra-pulmonary TB only; if the new NICE guidelines [13] are followed, and household contact tracing around extra-pulmonary TB cases is not performed, there will be a missed opportunity to identify subsequent cases in 25% of households, potentially leading to further transmission from undiagnosed pulmonary cases. The considerable delay before subsequent cases in households are diagnosed and start treatment suggests improvements could be made in speed of identifying contacts and conducting screening. Our finding that no lineage of TB was associated with recent household transmission, with no increased transmissibility in the Beijing lineage compared to others, suggests that the lineage need not impact contact tracing efforts; a study from Canada supports this finding [23]. Finally, we found household transmission was more common for cases born in Somalia or Romania and certain UK-born ethnic groups, suggesting that targeted interventions, such as raising awareness within these high-risk communities, and overcoming barriers to effective contact tracing could have an impact on reducing transmission of TB in England.

The Collaborative Tuberculosis Strategy for England 2015–2020 cites contact tracing as a key activity for TB control requiring strengthening [24]. Actions could include more home-based visits, improved awareness and education, and should consider the sociocultural aspects of health-seeking behaviour. Our study suggests such improvements could reduce not only the number and rate of TB in UK and non-UK-born populations, but also the transmission of TB within England.