Latent Tuberculosis

Latent tuberculosis and the risk of active tuberculosis

It has been estimated by WHO that up to one third of the world’s population (2 billion) have latent tuberculosis. Latent tuberculosis has been defined as a state in which there is persistent bacterial viability, immune control of the bacteria and with no evidence of clinical active tuberculosis. Studies have shown that between 5 to 15% of those with latent tuberculosis will “reactivate” during their lifetime and develop active disease. “Reactivation” of the Mycobacterium tuberculosis (TB) bacteria resulting in active disease accounts for the majority of “new cases” of active TB detected annually.

Reactivation of Tuberculosis

The process of reactivation is likely to depend on the interplay between bacteria and host factors. This interaction is likely to be a continuum and the “latent” state is maintained when the host immune responses predominate and “disease” occurs when bacterial replication exceeds a certain threshold that results in disease.

  • Bacteria Factors:

The initial bacterial load from the index patient is thought to be a factor in determining the likelihood of developing active disease. There may be different strains of TB that are more likely to cause active disease. These postulates remain to be clearly elucidated by scientific studies.

  • Host Factors:

Older patients have a higher risk of reactivation of TB and this is likely to be related to waning immunity associated with ageing. In Singapore, the incidence of TB for the general population in 2013 was 36.9 per 100,000 but the incidence is higher at 64.1 per 100,000 in those between age 60-69 years old and increasing further to 148.3 per 100,000 in those aged >80 years old. HIV infected patients who have latent TB and who have not received anti-retroviral treatment have a 10% annual risk of TB. This contrasts to the approximate 10% life time risk for latent TB in the general population. Other medical conditions like diabetes, alcoholism, renal disease, cancer are additional factors for reactivation of TB. Medications that suppress the immune system may increase the rate of reactivation. These include systemic corticosteroids, monoclonal antibodies against tumor necrosis factor alpha (TNF-α), certain cancer chemotherapy agents and medications taken by organ transplant recipients.

With reactivation, there is active disease and the patient will eventually develop symptoms of tuberculosis. The most common site of disease is the lungs and symptoms such as cough, sputum production, haemoptysis (blood in sputum) and breathlessness may develop. Other sites of involvement may be the lymph nodes (often presenting as persistent lumps in the neck), bones and joints and the gastrointestinal tracts (presenting as diarrhoea and abdominal pain). Patients with untreated tuberculosis of the lungs are the source of ongoing transmission. Up to 1/3 of household contacts may become infected with the TB bacteria and the majority will develop latent TB.

Diagnosis of Latent TB

Screening for TB is usually done if you are exposed to an index patient with pulmonary tuberculosis. Usually, the index patient will be a household contacts or work colleague sharing the same office area. First year university students who come from countries endemic with tuberculosis may also be screened for TB upon entry to the university. In addition, screening for TB may be a company policy for health care workers and expatriate staff posted to a country endemic for tuberculosis.

The tests that are usually done are the tuberculin skin test (TST) and the interferon-gamma release assays (IGRA) such as the Quantiferon TB test and the T-spot TB test. These tests indirectly measure TB infection by measuring the immune response to TB proteins. “Reactive tests” indicate that an individual has been exposed to TB. These tests are imperfect and each of them has false positive and false negative testing rates. These tests also cannot be used to determine if an individual who has been exposed to TB will progress to develop active disease. In addition, the tests cannot distinguish between latent tuberculosis and active tuberculosis.

Treatment of Latent Tuberculosis

The aim of treatment of latent TB is to prevent progression to active disease. This involves treatment with one or 2 TB drugs taken for 4-9 months. The drug regimens used and the duration recommended are based on research studies.

In contrast, when the patient has active tuberculosis, the treatment usually involves 4 drugs for the first 2 months (induction phase) followed by 2 drugs for another 4-7 months (maintenance phase) to control and eradicate the disease.

Patients with latent tuberculosis are not “infectious” and do not transmit the infection.

In healthy individuals, it is not mandatory to institute treatment for latent tuberculosis as the lifetime risk of developing active tuberculosis is 10%. Treatment should be considered in patients with high risk for reactivation such as patients prescribed with immunosuppressive agents, HIV infection etc.

At this present time, there are no commercial tests available to help us to determine when treatment for latent tuberculosis has been successful in removing the risk of active tuberculosis.

We hope that this article helps to clarify some common concerns and misconceptions about latent tuberculosis. If you continue to have doubts and need further clarification, please contact your family practitioner or arrange an appointment at our specialist clinics.

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