Focus on latent tuberculosis.
Pursuit of the ambitious targets set by WHO's End TB strategy in 2015 has led to a substantial upswing in interest in diagnosing and treating latent tuberculosis infection (LTBI) among high risk groups, and reports in 2016 by WHO and Eurosurveillance both emphasise that the programmatic management of LTBI must be scaled up if progress is to be made in combating tuberculosis. Most recently, the US Preventive Services Task Force updated its recommendation on LTBI screening, suggesting that it should be done in populations at increased risk, such as migrants from countries with a high tuberculosis burden and people living in homeless shelters or correctional facilities. Of all individuals with LTBI, roughly 5% 10% will go on to develop active disease. The rationale for targeting LTBI in settings of low tuberculosis burden is particularly strong, because in these settings up to 80% of incident tuberculosis cases could be due to reactivation of LTBI. As with all major public health interventions, political will and fi nancial investment will be key components of success, but these are not the only hurdles faced by programmes to combat LTBI. The fi rst problem lies with diagnosis, since there is currently no gold standard test for latent tuberculosis. The tuberculin skin test has limited sensitivity and specifi city it may give false positive results in people who have previously received BCG vaccination, and false negative results in people with impaired T cell function. It is, however, cheap and easy to use in resource poor settings. Interferon g release assays are more specifi c than the tuberculin skin test but with a similar sensitivity, and the results are not infl uenced by BCG vaccination status; however, they can be expensive, thus restricting their use in resource poor settings. Results of two phase 3 trials of the novel C Tb test, presented at the American Thoracic Society Congress in May, 2016, suggest that C Tb has similar sensitivity and specifi city to Interferon g release assays and is more fi eldfriendly. These fi ndings suggest that better diagnostic tests might be on the horizon, but when they will be widely available is unknown. There are also diffi culties in retaining patients in LTBI programmes. Groups who are particularly at risk of acquiring LTBI include migrants from countries with a high tuberculosis burden, close contacts of people with active tuberculosis, and people particularly vulnerable to infection (eg, people with HIV or those being treated with tumour necrosis factor antagonists) Once atrisk populations have been identifi ed, they need to be screened, to undergo a medical assessment, and be started on drug therapies and followed up. In a study published in The Lancet Infectious Diseases in August, 2016, Hannah Alsdurf and colleagues analysed the cascade of care in LTBI and showed that patients were lost to follow up at several stages. The investigators did a systematic review and meta analysis of 58 studies including 748 572 people from both low income and high income countries, and noted that, of individuals deemed eligible for screening, only 72% were actually tested. This fi gure also hides heterogeneity: 86% of those intended for screening because they were vulnerable to infection were tested; however, among migrant groups the corresponding fi gure was only 43% Losses occurred at other stages in the process as well. For example, only 78% of individuals who were referred because of a positive test result actually completed a medical assessment, and only 61% of those who started treatment actually completed it 50% of those with a medical indication, 14% of migrants, and 10% of people screened in the general population. The results show that LTBI programmes require robust systems to track and monitor patients. Eff orts must be made to engage migrant communities in particular groups that are known to have diffi culties in accessing health care resources. Up to date fi gures on the burden of LTBI would also be benefi cial. The prevalence of LTBI is often quoted as around one third of the total global population, although this WHO estimate is now out of date, having been calculated in 1997. Accurate estimates of LTBI prevalence in diff erent geographical regions and diff erent populations will help to target interventions and increase their effi ciency. Despite the hurdles that must be overcome, the recent fl urry of activity around LTBI suggests that the international health and research communities are already mobilising to meet the demands of the End TB strategy. Key priorities now will be to better engage the growing number of at risk migrants and to build eff ective LTBI screening and treatment programmes where they are most needed. The Lancet Respiratory Medicine For more on WHO's End TB strategy see http:/www.who. int/tb/post2015_strategy/en/
The Lancet. Respiratory medicine