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Despite good public health, tuberculosis is still prevalent today in Ireland. This is by it being the most lethal infectious disease in the world killing more than 1.5 million people annually, approximating to 4,100 deaths a day worldwide.
TB is caused by Mycobacterium tuberculosis (M. Tb). It is spread by small, airborne droplets dispersed when an infectious patient with TB coughs, sneezes, sings or even talks.
Anybody in contact with these droplets can either develop active or latent tuberculosis infection. This depends on the virulence of the mycobacterium strain and the host person’s immune defences.
What is latent tuberculosis infection and why is it relevant?
In most circumstances, an exposed person mounts an immune response which prevents active tuberculosis. Infection with M. Tb is arrested after the person’s cell-mediated immunity contains the bacteria within granulomas made from activated T cells and macrophages. This is latent tuberculosis infection (LTBI).
LTBI is not infectious and asymptomatic. A person cannot spread the infection to others.
Evidence has shown that risk of progression from LTBI to active TB infection is highest in selected risk groups:
- Patients initiating anti-TNF treatment like infliximab e.g. rheumatoid arthritis and inflammatory bowel disease patients
- HIV-positive individuals
- Patients on dialysis with end-stage renal failure
- Patients before or after organ/haematological transplantation
- Patients with silicosis
- Adults or children who had contact with patients with active pulmonary TB infection
Latent TB testing
Latent tuberculosis infection can be diagnosed using 2 methods:
1. Tuberculin skin test (TST).
This is also referred as the Mantoux test or the PPD test (purified protein derivative). This test is a 2-step process where the skin must be examined 48 to 72 hours after the test is done to measure an induration of response.
2. IGRA test or Quantiferon TB test.
This is a blood test involving interferon gamma release assays (IGRA).
In patients with evidence of previous BCG vaccination, Quantiferon TB test (IGRA) is more specific and equally sensitive to TST. False-positives are less likely with IGRA than TST.
Once again it is important to recognize that IGRA cannot differentiate between active tuberculosis and latent tuberculosis infection. A patient with a positive IGRA or TST should be referred to a physician capable of out ruling active tuberculosis infection by detailed clinical history, exam and chest radiography for signs of pulmonary TB (pulmonary opacification, cavitation, pleural effusions etc.)
M. Tb commonly causes both mortality and morbidity through active tuberculosis infection. This can manifest as primary TB, reactivation TB, endobronchial TB, or a tuberculoma.
Primary tuberculosis usually presents with fever and chest pain. Enlarged lymph nodes are common and present with retrosternal pain and interscapular dullness. Thoracic imaging may reveal hilar adenopathy, pulmonary opacification or even pleural effusions.
Reactivation of tuberculosis usually affects the upper lobes of the lung. Symptoms are protracted and result in weight loss, productive cough with blood occasionally (haemoptysis), breathlessness, night sweats, fevers, and severe malaise.
Diagnosis of active pulmonary tuberculosis infection
All patients suspected of having pulmonary tuberculosis should give at least 3 sputum specimens for acid-fast bacilli smear microscopy. False-negative results are sufficiently common so diagnostic nucleic acid amplification testing (NAAT) should be simultaneously done on the initial respiratory sputum specimens of patients suspected of pulmonary TB. NAAT testing means the patient’s sputum is amplified to detect M. T- specific nucleic acid sequences. In Ireland, diagnostic NAAT is done by TB Xpert MTB/Rif test which also screens for rifampicin resistance.
Note in AFB-smear negative patients with suspicious features for pulmonary TB, a positive NAAT test can be used as presumptive evidence of pulmonary TB.
A positive NAAT test unfortunately does not differentiate between viable and non-viable mycobacterium tuberculosis bacteria. The gold standard for diagnosis of active tuberculosis infection is culture of M. Tb.
Culture drug susceptibility testing (DST) for isoniazid and rifampin is done as routine on all mycobacterium tuberculosis complex isolated in culture. Note it can take more than 2 weeks for an isolate to grow sufficiently for DST.
How is TB treated?
Aim of treatment is both treatment-completion and treatment-cure. Cure from pulmonary TB is defined as a patient with bacteriology-confirmed TB who is AFB smear- or culture-negative at the end of treatment.
Treatment failure refers to a patient whose sputum smear or culture is positive at month 5 or later during treatment. Treatment completion is a TB patient who completes treatment without evidence of failure but with no record to show that sputum smear of culture results in the last month of treatment.
TB is treated with antibiotic tablets. This is usually for a six-month period. Sometimes, a longer course of treatment is needed. It depends on which parts of the body are affected. To make it easier for a patient to take their medications, combination tablets are now available. Rifater is usually the standard prescribed tablet for the initial 2 months’ treatment phase. This is a combination of rifampin, isoniazid and pyrazinamide. Rifater is given with ethambutol and pyridoxine (a vitamin B6) tablet. For the continuation phase, Rifinah which is a combination of rifampin and isoniazid is used.
IT IS VERY IMPORTANT THAT YOU NEVER MISS YOUR TABLETS. Always make sure to have enough tablets in the house. Remember to fill your prescription on time. If you forget your tablets in the morning, take them later that day. If you take your tablets as prescribed, then TB can be COMPLETELY CURED. However, if you miss your tablets, TB bacteria can become resistant to the antibiotics. This makes the infection much more difficult to treat. The doctor will let you know how long to take the treatment for. The full course must be completed, even if you are feeling well.
Are there any problems with the TB therapy tablets?
Tablets used to treat TB do not normally cause problems.
Some people may experience side effects. Nausea and vomiting can occur. This usually settles after a few days. If necessary, medication to improve the nausea can be taken.
Patients can expect orange discoloration of urine and tears throughout their treatment period as it is a recognized effect of rifampin; one of the antibiotics involved. Rifampin (contained in both Rifater and Rifinah) can also discolour contact lenses.
Sometimes, the tablets can cause inflammation in the liver. You will need to have blood tests done to monitor the liver. If you develop a yellow colour (jaundice) in the skin or eyes while on treatment, let your doctor know straight away.
Other side effects can include rash, dizziness, blurring of vision and pins and needles or numbness in the hands or feet. Let your doctor know if you experience any of these problems. The medication can then be changed. The medication will not be stopped, however, until the full treatment is finished. Let your doctor know if you are taking the oral contraceptive pill. The TB tablets can make the pill less effective. Alternative contraception can be prescribed.
Can a patient continue working?
People with mild infection may not have to take any time off work. Some people may have to stay off work for a short time. This is when they are infectious, or if they need to get their strength back. Your employer will be told that a full recovery from the infection is expected.
Will I have many hospital visits?
At first, after you have been diagnosed as having TB, you will have to attend the clinic in the hospital every 3 to 4 weeks. You will have to attend less often after that. At the clinic, your progress will be assessed. This is done by checking your weight, doing chest x-rays and, sometimes, testing your phlegm (to see if the bacteria are still there). Once treatment has been finished, you will be seen once or twice a year for two years. This is to make sure everything is ok. After this, you will not need to be seen unless you are feeling unwell.
Is there a worry of drug-resistant tuberculosis?
There has been an emergence of drug resistant TB over the last decade. Clusters of multidrug-resistant TB (MDR TB) and extensively resistant TB (XDR TB) have led to increased emphasis on compliance and treatment completion.
MDR TB is M. Tb strains which are resistant to isoniazid and rifampin. XDR TB refers to M. Tb strains which are also resistant to fluoroquinolones and at least one second-line injectable agent (amikacin, capreomycin, or kanamycin).
Expert consultation with a specialist experienced in tuberculosis management should be obtained for all cases of drug-resistant tuberculosis.
I got the BCG vaccine, does that mean I am immune from TB?
The BCG vaccine confers little protection against TB in adults. It is most effective in infants and young children. Evidence of previous BCG vaccination will be remnants of a small flat scar, bump or papule on your upper forearm.
Previous BCG vaccination can confer a positive reaction after a tuberculin skin test because of cross-reactivity with the purified protein used for the skin test.
Is there chance of a vaccine in the pipeline?
Since its formulation in 1921, the Bacillus Calmette–Guérin (BCG) vaccine is the only licensed vaccine against infection with active tuberculosis. Most European countries have stopped recommending the BCG vaccination due to its lack of efficacy in a non-selected population. In Ireland, the current advice by the National Immunization Advisory Committee NIAC and HIQA as of March 2017 is not to routinely administer the BCG vaccine to babies in Ireland.
There are currently at least 13 trial vaccines against tuberculosis in clinical trial phase. Broadly these vaccines are utilizing 3 modes of inducing immunity via whole-cell or lysates of mycobacteria, viral vector vaccines and adjuvanted recombinant protein vaccines. These vaccines are attempting prevention of active TB disease in infants, prevention of active TB in patients with LTBI, and prevention of active TB disease in uninfected individuals among other attempts at replicating the success of the BCG vaccine.
Mycobacterium tuberculosis can travel through the body and infect any organ, and produce extrapulmonary TB. Peripheral lymph nodes and the lung lining (pleura) are the commonest sites for extrapulmonary TB. Other sites implicated are like the kidneys, the brain and its meninges, the spine and the growing end of the long bones.
Invasive procedures to biopsy tissue for histological examination and mycobacterial culture is recommended to diagnose extrapulmonary TB.
If obtaining fluid like cerebrospinal, pleural and peritoneal fluid is possible; the more fluid sent for analysis increases the likelihood of positive culture. Tuberculous infection of bodily fluids usually result in a raised fluid protein concentration, lymphocytosis and low glucose content. If renal TB is suspected, the first voided midstream urine specimen is still preferred.
All fluid should be sent for cell count and biochemical analysis, mycobacterial culture and measurement of adenosine deaminase levels and free IFN-gamma levels If possible.
Recent evidence also support that NAAT be performed on both tissue and fluid specimens used to diagnose extrapulmonary TB. A positive result can guide treatment decisions as a false-positive result is unlikely.