Latent tuberculosis infection: Update on provincial treatment guidelines

Tuberculosis (TB) is an infectious disease that typically affects the lungs and is spread from person to person through the air by droplets expelled when coughing or sneezing. This disease poses a global public health threat.[1] In 2016, about 10 million people fell ill with TB, and about 1.7 million died worldwide from the disease.[2] Despite efforts to eliminate it, TB is now the leading infectious-disease killer globally and the leading killer of people living with HIV.[3] 

Approximately one-quarter of the world’s population has latent (or dormant) TB, which means that people have been infected with the TB bacteria but the infection has not progressed to active disease.[2] Those with latent TB infection (LTBI) do not present with illness or symptoms and are not infectious. For some individuals, the bacteria can overcome the immune system defences and begin to multiply, resulting in the progression from LTBI to active TB disease.[4] It is estimated that about 5% to 10% of those infected with TB will develop active TB at some point in their lives.[4] The likelihood of this occurrence increases considerably for those with weakened immune systems and other comorbid illnesses. 

Treatment of LTBI can substantially reduce the likelihood of activation[5] and subsequent transmission, and is therefore a crucial component in preventing active TB disease. In BC, while treatment for LTBI is voluntary, an emphasis is placed on treating those infected within the previous 2 years, immigrants and refugees from high TB–prevalence countries, children under 5 years of age who’ve come into contact with TB, and those with risk factors that substantially increase the likelihood of progression to active TB disease—those with HIV infection or AIDS, chronic kidney disease, and organ transplants, and those taking high doses of immune suppressive therapy.

In BC, standard first-line treatment for LTBI has focused on 300 mg of daily self-administered isoniazid for 9 months. Alternatively, isoniazid can be given twice weekly through direct observed preventive therapy (DOPT) for 9 months as an option for vulnerable clients requiring intensive support to complete therapy. However, poor completion rates, in part due to the length of this treatment regimen as well as drug-induced liver disease, have been an ongoing challenge for some patients. An available but less widely used alternative to the isoniazid regimen has been 600 mg of daily self-administered rifampin for 4 months. Rifampin treatment of LTBI would typically be considered for those with intolerance to isoniazid, those exposed to an isoniazid-resistant organism, or those with medication interactions to isoniazid. A building evidence base suggests that rifampin treatment of LTBI is a safer and less-expensive alternative with excellent treatment completion rates. Rifampin treatment for LTBI will now be used as a first-line treatment regimen in BC. 

A third regimen option for LTBI is a combination of isoniazid and rifapentine. Provincial TB Services at the BC Centre for Disease Control has been able to obtain a 1-year access to rifapentine through Health Canada’s Exceptional Circumstances Access Program. Clients at the provincial TB clinics may be offered this once-weekly 12-week regimen of isoniazid (900 mg) and rifapentine (900 mg) (referred to as 3HP) as the newest LTBI treatment option. Currently, this regimen is only offered as DOPT to eligible clients receiving care at the Vancouver or New Westminster provincial TB clinics. Expanded use of 3HP to the rest of the province will be considered in the future. Updated LTBI treatment guidelines can be found in the TB manual put out by the BC Centre for Disease Control (www.bccdc.ca/resource-gallery/Documents/Communicable-Disease-Manual/Chapter%204%20-%20TB/TB_Manual.pdf).

Treatment of LTBI is a crucial aspect in the global flight to eliminate TB. Clients with untreated or incompletely treated LTBI remain at risk for active TB disease. Rifampin as a first-line treatment regimen, or other LTBI treatment regimens, may help improve provincial LTBI treatment completion rates. This will aid in the fight to eliminate TB. 
—Shaila Jiwa, BScN, RN, MScPPH
Senior Practice Leader, Clinical Prevention Services
BC Centre for Disease Control
—Victoria Cook, MD, FRCPC
Medical Head, Provincial TB Services
BC Centre for Disease Control

References

1.    World Health Organization. Global tuberculosis report, 2015. Accessed 6 April 2018. www.who.int/tb/publications/global_report/gtbr2015_executive_summary.pdf.

2.    World Health Organization. Tuberculosis [fact sheet], 2018. Accessed 6 April 2018. www.who.int/mediacentre/factsheets/fs104/en.

3.    World Health Organization. Global tuberculosis report. Geneva: World Health Organization, 2017. Accessed 9 April 2018. http://apps.who.int/iris/bitstream/handle/10665/259366/9789241565516-eng.pdf.

4.    US Centre for Disease Control. TB elimination: The difference between latent TB infection and TB disease [fact sheet], 2011. Access 9 April 2018. www.cdc.gov/tb/publications/factsheets/general/LTBIandActiveTB.pdf.

5.    Holland DP, Sanders, GD, Hamilton, CD, Stout, JE. Costs and cost-effectiveness of four treatment regiments for latent tuberculosis infection. Am J Respir Crit Care Med 2009;179:1055-1060.