You have tested positive for tuberculosis (TB) but not shown any symptoms for two years. Are those germs likely to persist and make you sick years later? Most likely not, suggests a study that has combed published research from over half-a-century on the incubation period of the TB bacterium and the time it usually takes to manifest into the disease.
Globally, nearly 10 million people developed TB disease in 2017 and about 1.7 billion people, or 23% of the world’s population, are estimated to have a “latent TB infection, and are at risk of developing active TB disease during their lifetime”, according to the World Health Organisation’s Global Health Report 2018, made public last week.
Advice to high burden nations
The canonical belief, it emerges from the study, that 40% of Indians may be infected with the bacterium is based on a “misunderstanding” and “simply wrong,” one of the researchers involved told The Hindu. She added that countries such as India with a high disease burden would do well to focus on treating active TB cases (that is those clinically confirmed and manifesting symptoms), than trying to stamp out latent TB.
These numbers, from which India’s latent-TB burden are also derived, are based on results from the popular diagnostic tests employed — the ‘skin test’ and the Interferon Gamma Release Assay, or IGRA (a blood test) — that only indicate whether a person had generated immunity in response to TB exposure. They do not say whether the germ lies latent or will manifest into active disease. “Most of them are not latently infected. They were infected at one time, cleared the infection and may even be somewhat protected against new infection,” said Lalita Ramakrishnan, one of the study authors and Professor of Immunology at the MRC Laboratory of Molecular Biology, University of Cambridge. “In short, the statement that 40% of Indians are latently infected is simply wrong, and based on confusing immunoreactivity to TB with latent infection.”
The conventional wisdom regarding TB — including the WHO’s — is that only about 5-10% of those infected by the bacterium will likely become sick by it. “We agree with this. The main conclusion of our study is that these 5-10% will develop TB within a few months to at most two years. Only a very small minority of these 5-10% will develop TB later than that,” the authors said in an e-mail. She and her co-authors (Marcel Behr from McGill University and Paul Edelstein from the University of Pennsylvania) do not specify how small that minority might be. But even accounting for the low numbers, that somebody might fall sick from an infection acquired, say decades ago, is higher in ‘low-incidence’ countries (such as Norway, Denmark and Canada) than ‘high transmission’ countries like India, suggests the paper that was published in the peer-reviewed British Medical Journal on August 23.
At 2.7 million cases, India has the most number of TB patients in the world. It accounts for 32% of global TB deaths among HIV-negative people, and for 27% of the total TB deaths in HIV-negative and HIV-positive people in 2017.
Data search
For their study, Ramakrishnan and her colleagues looked at evidence from studies from Denmark, Canada and the U.K. to conclude that the incubation period of TB has not noticeably changed over the decades. They did not find similar studies that looked at incubation rates in India, said Ramakrishnan. “The fact is that studies from 1948 to now show the same results, in Europeans (old studies) and in modern studies in London, Netherlands and also Canada — which were likely mostly non-European. So there is no reason to believe that TB incubation periods have changed over time or are different in different ethnic groups. Therefore, there is no reason not to extrapolate these findings to India,” said Ramakrishnan, who works on understanding the biology of tuberculosis by modelling it in zebrafish.
An independent researcher said that Ramakrishnan’s results did not challenge the current approach to treating TB in India. Active TB cases as well as those who lived in close proximity to them were the prime focus of India’s eradication efforts.
India’s focus
India has committed to eliminate the disease by 2025, requiring a reduction of 10% a year but, in 2017, it only managed a 2% reduction from the previous year.
“Treating active TB, HIV patients and children under-5 has been the traditional focus of the Indian programme,” said Srikanth Tripathy, Director, National Institute for Research in Tuberculosis, in Chennai, an Indian Council for Medical Research body. “But with the 2025 target, there is a focus on preventive treatment of those who are in contact with those testing positive. Evidence from India also shows that it is the first three years since testing positive that really matter.”
jacob.koshy@thehindu.co.in
