Almost a quarter of the world’s population is infected with ‘latent’ TB, according to a new mathematical modelling study by London School of Hygiene and Tropical Medicine.
Only about 10% of people with latent TB actually become ill with the active form of the disease because most people’s immune systems keep the disease dormant for life. But for people with weak immune systems the risk of becoming ill with the disease rises dramatically. People living with HIV are of special concern as they are 20 to 30 times more likely to develop active TB from a latent infection, according to the World Health Organisation.
However, it is not only people with weak immune systems who develop active disease, according to Dr Arne von Delft, from the organisation TB Proof. “This containment process is not well understood and it is currently not possible to predict who will become sick or when. Anybody who is exposed is at risk,” he said.
A study to estimate the global burden of latent TB has not been done for 20 years and for two decades it has been thought that a third of the world’s population was affected.
Although the new global estimates are lower, 1.7bn people are infected with latent TB including 100m children.
But in places like South Africa latent TB poses a significant threat because of the high number of people living with HIV in the country who are at increased risk of becoming ill and infectious. Additionally, latent TB rates in South Africa are much higher than the global average.
Two years ago the WHO released guidelines recommending latent TB be treated in countries with low TB burdens, which excludes South Africa. In high burden countries the WHO only recommends treating latent infection in people living with HIV and children younger than five who have been in close contact with someone with TB.
Von Delft said this is simply not enough. “We have approached the HIV epidemic aggressively, we have started treating people earlier and introduced preventative treatment for HIV and for TB in people living with HIV. But why are we so blasé about ramping up our TB response for everyone else? This is the leading infectious disease killer in the world and a leading cause of death in South Africa,” he said.
Additionally, there are no tools to identify if a latent TB infection is standard TB or drug-resistant TB (DR-TB). Von Delft suspects he is infected with latent DR-TB as he was exposed to this form of the disease when his wife fell ill in 2010.
But, even as a doctor working in the TB field, he has no options for treating himself – other than undergoing the two-year toxic treatment regimen used to treat active DR-TB – a major side-effect of which is deafness.
“Research into latent DR-TB is not a priority and considering the threat that poses to ending the epidemic – it’s a global embarrassment.” According to the new study, “even if all TB transmission stopped tomorrow, the current pool of latent infections alone would be enough to exceed the End TB global targets for TB control in 2035 and 2050”.
Background: The existing estimate of the global burden of latent TB infection (LTBI) as “one-third” of the world population is nearly 20 y old. Given the importance of controlling LTBI as part of the End TB Strategy for eliminating TB by 2050, changes in demography and scientific understanding, and progress in TB control, it is important to re-assess the global burden of LTBI.
Methods and Findings: We constructed trends in annual risk in infection (ARI) for countries between 1934 and 2014 using a combination of direct estimates of ARI from LTBI surveys (131 surveys from 1950 to 2011) and indirect estimates of ARI calculated from World Health Organisation (WHO) estimates of smear positive TB prevalence from 1990 to 2014. Gaussian process regression was used to generate ARIs for country-years without data and to represent uncertainty. Estimated ARI time-series were applied to the demography in each country to calculate the number and proportions of individuals infected, recently infected (infected within 2 y), and recently infected with isoniazid (INH)-resistant strains. Resulting estimates were aggregated by WHO region. We estimated the contribution of existing infections to TB incidence in 2035 and 2050.
In 2014, the global burden of LTBI was 23.0% (95% uncertainty interval [UI]: 20.4%–26.4%), amounting to approximately 1.7 billion people. WHO South-East Asia, Western-Pacific, and Africa regions had the highest prevalence and accounted for around 80% of those with LTBI. Prevalence of recent infection was 0.8% (95% UI: 0.7%–0.9%) of the global population, amounting to 55.5 (95% UI: 48.2–63.8) million individuals currently at high risk of TB disease, of which 10.9% (95% UI:10.2%–11.8%) was isoniazid-resistant. Current LTBI alone, assuming no additional infections from 2015 onwards, would be expected to generate TB incidences in the region of 16.5 per 100,000 per year in 2035 and 8.3 per 100,000 per year in 2050. Limitations included the quantity and methodological heterogeneity of direct ARI data, and limited evidence to inform on potential clearance of LTBI.
Conclusions: We estimate that approximately 1.7 billion individuals were latently infected with Mycobacterium tuberculosis (M.tb) globally in 2014, just under a quarter of the global population. Investment in new tools to improve diagnosis and treatment of those with LTBI at risk of progressing to disease is urgently needed to address this latent reservoir if the 2050 target of eliminating TB is to be reached.
Rein MGJ Houben, Peter J Dodd