UK screening for latent TB is failing

Revision of guidelines for the screening of migrants to the UK for latent tuberculosis (TB) could prevent a substantial number of cases of active disease, investigators report in the April 21^st  edition of The Lancet Infectious Diseases.

Current guidance recommends that adult immigrants aged 16 to 35 should be screened for latent TB only if they come from a country with a TB prevalence of 500 cases per 100,000.

The investigators showed that screening at lower prevalence thresholds would identify substantially more cases of latent TB and be cost effective.

“Our analysis suggests that policy could be modified…to substantially reduce tuberculosis incidence while remaining cost effective,” comment the authors.

TB notifications in the UK increased by 46% between 1998 and 2009. Most of these cases involve patients who were recent immigrants.

UK guidelines state that all individuals from countries with more than 40 cases of TB per 100,000 who are coming to live in the UK for six months or more should be screened for active TB using chest x-rays at the port of entry.

Screening for latent TB (tuberculosis which is not currently, but could potentially cause disease) is recommended for children from countries with a TB incidence of 40 or more cases per 100,000.

Adults aged 16-35 should also be tested for latent disease if their country of origin has a TB incidence of at least 500 cases per 100,000.

Screening is currently a two-step process. This involves a tuberculin skin test, followed by a confirmatory interferon-gamma release assay (IGRA) blood test.

Investigators wished to see if screening using IGRA tests by themselves at lower incidence thresholds would increase the number of latent infections detected, and if this screening strategy would be cost effective.

Their study sample consisted of 1229 recent migrants who were tested at local TB services in Westminster, London; Leeds, Yorkshire; and Blackburn, Lancashire between 2007 and 2009.

Children under the age of 16, and adults aged under 35 were included in the study. Patients with a positive screen were provided with appropriate chemoprophylaxis. The over 35s were not included in the study as the risks of chemoprophylaxis outweigh the possible benefits.

The majority of individuals were from setting with a high incidence of TB, such as the Indian subcontinent (60%) and sub-Saharan Africa (20%).

IGRA results were positive for 20% of patients. This included 19% of children; 15% of individuals aged 16-25; and a quarter of those aged between 26 and 35.

Higher TB incidence in the immigrants’ countries of origin were significantly associated with an increased risk of latent infection (p = 0.0006). Other risk factors included male sex (p = 0.046) and older age (p < 0.001). In total, 87% of latent TB infections involved patients from sub-Saharan Africa or the Indian subcontinent.

Had the current guidelines been used, only 22% of the study population would have been eligible for screening. Moreover, 71% of cases of latent TB would have remained undiagnosed.

“If we had applied national guidance…only 29% of latent infections would have been identified, leaving nearly three-quarters (mostly from the Indian subcontinent) undiagnosed and at risk of developing the disease and possibly infection others,” emphasise the authors.

However, decreasing the incidence threshold to 150 cases per 100,000 would have meant that 85% of individuals were eligible for screening and that 92% of all latent infections would have been diagnosed.

For children, the most cost-effective strategy was to start screening at an incidence of 40 cases per 100,000, and for adults the threshold was 250 cases per 100,000.

The later would involve a cost of £17,956 per case of active TB prevented. However, lowering the threshold to 150 cases per 100,000 would lead to the detection of most cases of latent disease. This would cost just £3,000 more per case than the most cost-effective strategy.

“This second strategy would encompass individuals from many Asian countries who are currently excluded, including those form the Indian subcontinent who form a large proportion of immigrants to the UK,” note the investigators.

They conclude, “current guidelines miss most imported cases of latent tuberculosis but screening for latent infection can be cost effectively implemented at an incidence threshold that identifies most immigrants with latent infection, thereby preventing substantial numbers of future cases of active tuberculosis.”

Pareek M et al. Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis. The Lancet Infectious Disease, online edition, doi: 10.1016/S1473-3099(11)70069-x, 2011.