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

Abstract

Background: We estimate the proportion of tuberculosis (TB) in England due to recent household transmission, identify factors associated with being a household transmitter, and investigate the impact that identification of a case has on time to treatment of subsequent cases. Methods: TB cases notified between 2010 and 2012 in England in the same household as another case were identified; 24 locus MIRU-VNTR strain typing (ST) was used to identify household cases with likely recent transmission. Treatment delay in index and subsequent cases was compared. Risk factors for being a household transmitter were identified in univariable and multivariable analyses.Results: Overall, 7.7% (1849/24,060) of TB cases lived in a household with another case. We estimate that 3.9% were due to recent household transmission. ST data was unavailable for 67% (1242) of household pairs. For those with ST data, 64% (386) had confirmed, 11% probable (66) and 25% (155) refuted household transmission. The median treatment delay was 65 days for index cases and 37 days for subsequent asymptomatic cases. Risk factors for being a household transmitter included being under 25 years old, UK-born with Black African, Indian or Pakistani ethnicity, or born in Somalia or Romania. Conclusions:This study has a number of implications for household TB contact tracing in low incidence countries, including the potential to reduce the diagnostic delay for subsequent household cases and the benefit of using ST to identify when to conduct source contact tracing outside the household. As 25% of TB cases in households had discordant strains, households with multiple TB cases do not necessarily represent household transmission. The additional fact that 25% of index cases within households only had extra-pulmonary TB demonstrates that, if household contact tracing is limited to pulmonary TB cases (as recently recommended in UK guidelines), additional cases of active TB in households will be missed. Our finding that no lineage of TB was associated with recent household transmission and with no increased transmissibility in the Beijing lineage compared to others, suggests that the lineage need not impact contact tracing efforts. Improvements in contact tracing have the potential to reduce transmission of TB in low incidence countries.

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London

“…Similar patterns are observed in Birmingham,16 17 and in both cities, the prevalence of disease among contacts of ETB cases was higher than the prevalence of disease among migrants eligible for pre-entry screening18 and more than 10 times higher than the NICE threshold for new entrant screening 17. Additionally, studies have shown only 25% of pairs of cases sharing an address in the UK,19 and 20% of case-contact pairs in London20 had different Mycobacterium tuberculosis isolates, implying the risk of disease in household contacts is high irrespective of whether transmission has occurred. This suggests that the fact that ETB cases are not infectious may not be a valid justification for not screening their contacts.…”

A model of tuberculosis clustering in low incidence countries reveals more transmission in the United Kingdom than the Netherlands between 2010 and 2015

“…A comparison of transmission, control measures and outcomes could elucidate the difference we observed between the UK and the NL. These would include the efficiency of contact tracing in the UK [26] and the NL [27], household transmission [13], and different transmission rates between migrant groups [22].…”

“…Furthermore, cases infected by indistinguishable strains may be epidemiologically unrelated, due to infection with a common strain [11]. Instead, genotyping is often used to rule out transmission, for instance between household members infected with different strains [12,13]. In low incidence countries, distinguishable strains are used to estimate the fraction of cases that are not due to recent transmission, but due instead to the reactivation of existing infections or cases infected elsewhere [14].…”

A model of tuberculosis clustering in low incidence countries reveals more on-going transmission in the United Kingdom than the Netherlands between 2010 and 2015

“…A comparison of transmission, control measures and outcomes could elucidate the difference we observed between the UK and the NL. These would include the efficiency of contact tracing in the UK (29) and the NL(30), household transmission (12), and different transmission rates between migrant groups (25).…”

“…Furthermore, cases infected by indistinguishable strains may be epidemiologically unrelated, due to infection with a common strain (10). Instead, genotyping is often used to rule out transmission, for instance between household members infected with different strains (11,12).…”