Shortness of breath, fever and exhausting fits of coughing with bloody sputum from the lungs. Tuberculosis is a serious infection that kills 1.5 million people worldwide annually.

In Denmark, the risk of getting tuberculosis is small – with less than 400 notified cases a year. However, routine screenings in the country's prisons and among HIV patients and socially marginalised groups could be beneficial. This is shown by a new analysis from Aarhus University.

Together with a research team, Medical Student Anders Solitander Bohlbro is the man behind a meta-analysis of all screening studies for active tuberculosis published over the past twenty years. The analysis provides grounds to redefine the current recommendations from the World Health Organization WHO, which currently strongly recommends screening only in patients with HIV, close contacts of tuberculosis patients, and people who have been exposed to silica dust in connection with their work.

Tuberculosis is the infectious disease that kills the highest number of people worldwide. However, effective treatment is available, and the UN therefore aims to put an end to the global tuberculosis epidemic by 2030. To do this, everyone with the disease needs to be identified, and right now it is estimated that only 70 per cent are found. Better strategies therefore need to be developed for finding each individual case of tuberculosis.

Enormous benefit from screening

The researchers from Aarhus have tried to find out whether there is evidence to expand the recommendations and test more groups. And there is – especially in Africa and South- and Central America, but also in high-income countries such as Denmark.

By comparing the results from 197 scientific studies of tuberculosis screening conducted over the past twenty years, and then dividing the studies into groups according to geographical region, screened population groups and established indicators of tuberculosis burden in the countries where the studies were conducted, the researchers have found that there are more infected patients than the WHO estimates.

"The study emphasises that there is an substantial benefit of screening for tuberculosis among at-risk groups in countries with a high incidence of tuberculosis – but that it is also a good idea to screen vulnerable groups in countries with an otherwise low incidence of the disease. In addition, the study provides grounds for considering recommending screening of the general population in countries with a generally high incidence of tuberculosis, something that has been discouraged by the WHO since 1974. This should influence on the global guidelines defined by the WHO," says Anders Bohlbro.

X-ray screening should be used more

Screening the general population in countries with a high incidence of tuberculosis will on average identify 504 undetected tuberculosis patients per 100,000 screened.

In countries with a low incidence such as Denmark, screening will on average identify 1,122 undetected tuberculosis patients per 100,000 drug addicts, 1,993 per 100,000 contacts of tuberculosis patients, and 905 cases for every 100,000 screened among marginalised groups .

The study therefore indicates that countries with a low overall incidence of tuberculosis, such as Denmark, will find a high incidence of the disease, if certain at-risk groups are tested.

"Tuberculosis screening of certain groups of socially disadvantaged people is already part of the strategy in some cities in Denmark – but not among prisoners, who are at risk when it comes to tuberculosis. It could be relevant to test for tuberculosis in prisons, for example in connection with the hepatitis screenings already in place," says Associate professor and Specialty Registrar Christian Wejse, who has been the project’s supervisor.

He adds that here in Denmark we could also benefit from a more systematic approach to testing new HIV infections for the dreaded lung disease.

"A proportion of HIV infected people in Denmark come from countries with a high incidence of tuberculosis. If you have a poorly functioning immune system due to HIV, being examined for tuberculosis when you’re being tested anyway is essential. It is part of the national recommendations, but it isn’t consistently done everywhere," says Christian Wejse.

“X-ray screening in particular should be used more. In fact, there is an X-ray bus in Gentofte that is used too little, and perhaps it would be relevant to bring it into play among marginalised groups in Denmark," he points out.

Facts about tuberculosis

• Denmark stopped vaccinating against tuberculosis in the 1980s. Today, it is recommended for children who are staying in risk areas for a longer period of time.
• Tuberculosis is treated with four different types of antibiotics over six months.
• Each year, ten million people get tuberculosis and 1.5 million die from the disease.

Facts about the study

• The research group has reviewed screening studies for active tuberculosis published over the past twenty years – a total of 197 studies with more than 12 million total screenings and 53,000 cases.
• The researchers have conducted a systematic review and meta-analysis of the screening results and have constructed a factor which compares the screening results against the WHO-estimated prevalence (Bohlbro Factor). This factor has never been used previously and makes it possible to estimate the added value of screening compared to existing case-finding strategies as well as the excess burden of tuberculosis in certain groups.
• Most countries focus on what is called passive case finding, in which the patient is diagnosed with symptoms after they themselves have contacted a healthcare professional. An alternative to this is active case-finding, where cases are identified by screening either specific groups or whole populations. The study concludes that this would be beneficial in many countries.
• The results suggest that screening recommendations should be extended so they, as a minimum, include poor and marginalised groups, prisoners and drug addicts, and that screening of the general population could be considered in countries with a high background risk of tuberculosis.
• The result has just been published in the prestigious European Respiratory Journal: https://erj.ersjournals.com/content/early/2021/03/18/13993003.00090-2021
• The study is funded by the Aarhus University Research Foundation. 

Contact

Stud.med. Anders Solitander Bohlbro
Department of Clinical Medicine, Aarhus University
Mobile: 91 11 79 84
Mail: asb@clin.au.dk

MD and Associate Professor and  Christian Morberg Wejse
Department of Public Health at Aarhus University and Department of Infectious Diseases at Aarhus University Hospital
Mobile: 51 94 45 19
wejse@ph.au.dk