Drug therapy and diagnostic techniques for tuberculosis continue to be developed. NICE guidance offers a standard approach to managing this infection
Miles Jarvis, MA, BSc, DipHE, DipTropN, RN (adult), is TB specialist nurse, Royal Bournemouth Hospital.
Jarvis M (2010) Tuberculosis 2: exploring methods of diagnosis, treatment regimens and concordance. Nursing Times; 106: 2, early online publiction.
The second in this two-part unit on TB examines diagnosis and treatment options. Part 1 outlined background on epidemiology and control of this disease.
This part, part 2, draws on the clinical guidance and standards set out by NICE (2006). Modern diagnostic methods are discussed and the standard recommended treatment regimen is outlined.
Keywords Tuberculosis, Respiratory care, Treatment regimens
- This article has been double-blind peer reviewed
1. Understand the current methods for diagnosing tuberculosis.
2. Be familiar with the current short course standard treatment regimen advocated by NICE (2006).
As outlined in part 1 of this unit, tuberculosis (TB) is a major global public health problem, and has been estimated as being responsible for over a thousand million deaths in the 19th and 20th centuries (Ryan, 1992). The search and discovery of a cure has been described as changing human history (Ryan, 1992).
This part, part 2, outlines how TB is now diagnosed and treated, and briefly examines treatment strategies, such as directly observed therapy (DOT) and assessment of treatment adherence.
As with any clinical condition, diagnosis begins with clinical suspicion and a good history. The main signs and symptoms of TB were outlined in part 1 of this unit. However, these can be non-specific, and mimicked by other conditions, including malignancy and other pulmonary conditions (Schluger, 2008). Failure to consider TB as a differential diagnosis can delay correct treatment, and puts others at risk as the risk of infectivity increases with disease progression.
NICE (2006) guidelines provide clear criteria for diagnosing pulmonary and non-pulmonary TB. The suspected site of the TB infection clearly guides which investigations are most relevant.
A chest X-ray is a vital investigation in the diagnosis of pulmonary TB (Fig 1), and to rule out pulmonary involvement in cases of non-pulmonary disease. However, it is important to consider that people who are immunosuppressed (such as those with HIV infection) may present with very different radiological features. Furthermore, a recent study found that 9% of patients diagnosed with pulmonary TB had a normal CXR (Pepper et al, 2008).
Imaging such as computerised tomography (CT) or magnetic resonance imaging (MRI) scanning is also important in diagnosing and assessing non-pulmonary TB, particularly in infection affecting the bones and joints, gastrointestinal or genitourinary tracts and disseminated (including miliary) TB. Ultrasound is also used to allow guided tissue sampling, and can give suggestive appearances of TB (Ormerod, 2008). Finally, echocardiogram is recommended to diagnose TB of the pericardium (NICE, 2006).
Sputum examination is the mainstay of pulmonary TB diagnosis, usually expectorated sputum collected on three consecutive days (Schluger, 2008). Collecting three samples has been shown to result in an improved yield in confirming the diagnosis of TB.
Sputum is examined by microscopy for the presence of acid fast bacilli (bacteria that are acid fast when stained for examination under a microscope). Their presence is usually synonymous with mycobacteria (Pratt et al, 2005). This does not confirm Mycobacterium tuberculosis, but demonstrates that mycobacteria are present in the sample. These samples are known as smears, and would be described as “smear positive” or “smear negative” depending on the result. If proven to be M. tuberculosis, a positive smear indicates that the patient has infectious pulmonary TB. Staff should request “AFB” on the microbiology form, as the staining methods differ from those for other microscopy examinations.
However, negative sputum smears do not eliminate the diagnosis of TB. Samples are then placed in a culture to incubate the mycobacteria present. Various culture media can be used, and results are available in 2-12 weeks to identify the mycobacteria and determine drug sensitivities depending on the culture technology used.
More rapid diagnostic testing is available in certain situations, such as before a major contact tracing exercise or if multidrug resistant TB (MDR-TB) is suspected (NICE, 2006). These molecular diagnostic tests are typically carried out in regional mycobacteria reference laboratories, and provide rapid identification of the mycobacteria and whether their genotype is likely to be resistant to rifampicin. This is an antibiotic used to treat TB, and resistance to it is a recognised marker for MDR-TB (Grant et al, 2008).
Growing the mycobacteria in culture is the “gold standard” of TB diagnosis, as this method has a very high sensitivity and specificity (Schluger, 2008). This allows identification of the species of mycobacteria, and importantly to which antibiotics the organism is sensitive. With the increase in MDR- and XDR-TB, the ability to determine drug sensitivities is crucial.
If patients are suspected of having a pulmonary TB infection and are unable to expectorate sputum spontaneously, then induced sputum may be considered, or fibreoptic bronchoscopy. The latter is useful where there is diagnostic uncertainty (Schluger, 2008). Children who are unable to produce sputum may have gastric washings taken, and this is a well established technique. However, it is now thought that yield of bacilli may be higher in induced sputum (Schluger, 2008).
Other techniques for obtaining samples to diagnose pulmonary TB include pleural biopsy/aspirate, lymph node biopsy, transbronchial needle aspiration and endoscopic ultrasound needle aspiration.
Other clinical specimens
Specimens are usually obtained to diagnose non-pulmonary TB, depending on the suspected site of infection. These commonly include: biopsies of the affected site (such as lymph nodes, skin or bowel); examination of cerebrospinal fluid; and aspiration of fluid (such as ascites). Early morning urine specimens are also examined to assist with the diagnosis of genitourinary TB.
It is vital that specimens are sent to microbiology so they can be examined for the presence of AFBs and placed into culture. As outlined above, this is crucial to identify any mycobacteria that are present and drug resistance.
The treatment of TB (both pulmonary and non-pulmonary) is highly evidence based, and is becoming standardised across the world. As outlined in part 1 of this unit, the basic principle of TB control is to establish a diagnosis and initiate treatment rapidly (Hopewell et al, 2008).
While the search for a cure for TB lasted for centuries, the discovery of streptomycin in 1948 began the modern era of chemotherapy for treating TB. Today, the treatment of TB requires combination therapy of a number of antibiotics (Peloquin, 2008). The anti-TB drugs used today include those only used for mycobacterial infections (such as isoniazid and pyrazinamide) or those with broader application (such as rifampicin and streptomycin).
NICE (2006) provides clear guidance on the length and components of treatment for active pulmonary and non-pulmonary TB that has been found to be fully sensitive to all first line medication (that is, no drug resistance). Treatment for pulmonary TB consists of a six month course of rifampicin and isoniazid, supplemented in the first two months by pyrazinamide and ethambutol. There are therefore two stages to what is known as the standard recommended regimen (NICE, 2006). The first stage consists of two months of “quadruple therapy”, followed by four months of “dual therapy” (rifampicin and isoniazid). For full details on prescribing, practitioners should consult the British National Formulary (2009) and NICE (2006).
Box 1 outlines the four main drugs used to treat fully sensitive TB.
Box 1. Four anti-TB drugs in the NICE (2006) standard recommended regime
- Rifampicin: introduced in 1967, is one of the most important drugs used in the treatment of TB. It is bactericidal against M. tuberculosis and is metabolised in the liver.
- Isoniazid: one of the most important anti-TB drugs, along with rifampicin. First used against TB in 1951, it is highly active against M. tuberculosis. As with rifampicin, it has a bactericidal action and is metabolised in the liver.
- Pyrazinamide: it has important sterilising properties for use in the first two months of treatment, or for longer if drug resistance is established. It is particularly useful in treating TB meningitis due to good meningeal penetration (BNF, 2009). It is also metabolised in the liver, and serious liver toxicity may occur occasionally (BNF, 2009) (see adverse reactions below).
- Ethambutol: is bacteriostatic and is the fourth anti-TB drug used in quadruple therapy. Introduced in 1962, it inhibits synthesis of the mycobacterial cell wall. The dose is reduced in people with renal disease (BNF, 2009) (see below).
People with TB meningitis are given a 12 month course of treatment consisting of two months’ quadruple therapy, followed by isoniazid and rifampicin for the rest of the treatment. The use of glucocorticoids (such as prednisolone) is also recommended for the first 2-3 weeks of treatment, followed by gradual withdrawal (NICE, 2006).
People with peripheral lymph node, genitourinary, disseminated (including miliary), joint and bone TB or TB at any other siteare recommended to take the standard treatment regimen. Those with pericardial TB are also given glucocorticoids for the first 2-3 weeks of treatment, followed by gradual withdrawal. Steroids are advocated in certain situations to minimise the inflammation and tissue damage caused by the immune response to the mycobacterial infection (Humphries et al, 1994).
For specific details on the care of each group with non-pulmonary TB, see NICE (2006).
Possible adverse reactions
All anti-TB drugs can cause adverse reactions. These can occur in 10% of patients, with a substantial proportion requiring modification of drug therapy (Joint Tuberculosis Committee of the British Thoracic Society, 1998). Some of the more significant reactions are outlined below:
- Hepatotoxicity – may be caused by rifampicin, isoniazid and pyrazinamide (BNF, 2009). Liver function should be checked at the start of treatment and at two weeks, and then if clinically indicated (Joint Tuberculosis Committee of the BTS, 1998). Patients should be advised about the potential symptoms of hepatotoxicity;
- Optic neuritis – this is rare but a recognised toxic effect of ethambutol (Joint Tuberculosis Committee of the BTS, 1998). Baseline visual acuity should be measured, and the drug only prescribed to those who will be able to report any changes in vision or eye symptoms. Patients should be advised to discontinue therapy immediately if they develop deterioration in vision and promptly seek further advice. Early discontinuation of the drug is almost always followed by recovery of eyesight (BNF, 2009).
- Peripheral neuropathy – caused by isoniazid. This is preventable by giving prophylactic pyridoxine to those at high risk (such as those with diabetes, alcohol dependence, chronic renal failure, HIV infection or malnutrition) (BNF, 2009).
- Mild adverse reactions to rifampicin, isoniazid and pyrazinamide include nausea and vomiting;
- Rare reactions to rifampicin include shock, acute renal failure and thrombocytopenic purpura. In these cases the drug should be withdrawn and not reintroduced (Joint Tuberculosis Committee of the BTS, 1998).
Patients should have baseline blood tests (urea and electrolytes, full blood count, liver function and HIV) and visual acuity recorded. Liver function tests should be repeated at two weeks and then if clinically indicated. Patients should be advised about possible adverse reactions and symptoms of concern that should be reported to their clinician. It is a national recommendation that all patients with TB have an HIV test, and patients need to give their consent to this as with any other medical investigation (British HIV Association, 2008).
It is vital to take a good drug history as there may be significant interactions with TB treatment. Rifampicin is a potent enzyme inducer, and as such can accelerate the metabolism of concurrent medication. Importantly these include many antivirals, antifungals, warfarin, cardiovascular agents, oral contraceptives, drug treatment for diabetes, corticosteroids and so on (BNF, 2009). Those caring for patients receiving TB treatment should consult the BNF to ensure there is no likely interaction with medication already prescribed.
The Joint Tuberculosis Committee of the BTS (1998) and NICE (2006) guidelines recommended that TB cases should be managed by doctors with full training in and experience of the specialised care of people with the condition. These may be respiratory clinicians, although input from other specialists may be necessary depending on the site of infection.
NICE (2006) and the Joint Tuberculosis Committee of the BTS (2000) further advocated that TB services should include specialist nurses and health visitors, and specified the ratio of TB specialist nurses to case notifications as 1:50. The BTS et al (2009) also emphasised the importance of TB nurse specialists.
Treating MDR-TB and XDR-TB
While the treatment for fully sensitive TB is standardised to the regimen outlined above, the treatment for drug resistant TB is more individualised, depending on the resistances identified.
Treatment for MDR- and XDR-TB is more lengthy, difficult and expensive, and is not based on the same quality of randomised trials that support the standard drug regimen (Grant et al, 2008). However, treatment is likely to consist of the first line drugs to which the organism is sensitive, a quinolone (such as moxifloxacin), a daily injectable agent (such as streptomycin or capreomycin), and other second line agents to make up the number of drugs to four or five (Grant et al, 2008).
Nurses should consult Grant et al (2008) for details on MDR-TB, in particular the epidemiology, diagnosis and treatment of this increasing problem nationally and globally.
Directly observed therapy and treatment adherence
Adherence to treatment is a major determinant of outcome (Ormerod and Prescott, 1991). One way to help ensure patient adherence is directly observed therapy (DOT). This is where the ingestion of every drug dose is witnessed (Joint Tuberculosis Committee of the BTS, 1998). DOT forms part of a global TB control strategy, which emphasises other elements of management such as the need for political commitment and monitoring systems to allow successful TB programmes to be implemented (see www.who.int for further details).
DOT is generally given three times a week, which is as effective as once daily treatment, although there is an increased risk of adverse reactions (Joint Tuberculosis Committee of the BTS, 1998). A review of research comparing DOT and self administered treatment found similar outcomes in relation to cure and treatment completion (Volmink and Garner, 2003).
NICE guidance (2006) indicates that the use of DOT is not usually necessary in most cases of active TB. However, all patients should have a risk assessment for adherence and DOT should be considered for those with adverse factors such as their history of adherence, or street/shelter dwelling homeless people with active TB.
Adherence to TB treatment can be monitored by carrying out tablet counts and random urine tests. Less confrontational techniques include the use of patient treatment diaries, home visits and health education counselling (NICE, 2006). Ensuring education leaflets are available in the appropriate language or media is also imperative for effective patient advice.
Once a case of TB has been identified, notification to the local “proper officer” is compulsory under the Public Health Act 1984 (Joint Tuberculosis Committee of the BTS, 2000). This is usually the consultant in communicable disease control (CCDC). The purpose of notification is to ensure that contact tracing procedures are instigated, and to provide accurate TB surveillance data so that epidemiological trends can be monitored (Joint Tuberculosis Committee of the BTS, 2000).
Nurses should consult the Joint Tuberculosis Committee of the BTS (2000; 1998) and NICE (2006) guidelines, which outline in more detail the issues discussed here, and include topics such as infection control, contact tracing and BCG vaccination.
TB continues to be a global public health emergency, particularly given the relationship with HIV co-infection (Davies et al, 2008). Treatment regimens for TB continue to develop, with much research focused on areas such as new drug therapy, effective vaccination, and development of new diagnostic techniques. However, the fight against TB will continue to require global political commitment to tackle the medical and social factors contributing to this enduring epidemic.
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