Clinical Management of Pulmonary Tuberculosis in the UK

1. Clinical Management of Pulmonary Tuberculosis in the UK Adherence Lay Abstract Clinical Management • Drug adherence is key to successfully treating TB and avoiding the development of MDR TB. • To improve adherence6: • Involve the patient throughout their treatment. • Assign key workers to each patient and conduct random home visits and pill counts. • Carry out random urine testing. • Send frequent reminder letters regarding treatment. • Directly Observed Therapy (DOTS) • After completing a risk assessment for adherence, clinicians should consider DOTS for patients with a history of non-adherence, or if they are homeless or living in a shelter with active TB. DOTS is where a trained healthcare worker witnesses the ingestion of every dose of treatment. This ensures that patients are adhering to treatment and enables physicians to assess disease progression. Tuberculosis (TB) is a disease caused by bacteria. Pulmonary TB affects the lungs and it is spread when bacteria from sneezing and coughing enter the lungs. The body’s defence system fights the infection by surrounding the bacteriain the lungs and, as a result, most people do not develop any signs of the disease. If the body’s defence system is weakened, the bacteria can be triggered again and TB can develop. It is treated with a course of antibiotics. If a patient does not respond to these, they are a given different medication with Directly Observed Therapy. The BCG vaccine protects against TB, however, in the UK, only people at a high-risk of catching the disease are given this injection. In order for the disease to be successfully treated, it is essential that the antibiotics be taken regularly. First Line Pharmacological Management Shown inFigure 2 is the recommended six month four-drug regimen for active pulmonaryTB. This has been the gold standard for the last 15 years and has shown a >95% cure rate. Combination drugs are available to improve adherence. Patients whohavedifficulty with adherence are given Directly Observed Therapy and are considered for a thrice-weekly dosage. Over half of the clinics in the UK offering care for TB have a specialised and dedicated TB clinic.6 Second Line Pharmacological Management Rapid drug susceptibility testing is recommended for patients suspectedof having a resistant strain of TB. Second line treatment is given for positively tested patients. Treatment regimens last approximately 20 months in total, with 8 months of intensive therapy and consists of a minimum of five drugs.The main drugs recommended are shown inFigure 3. Treatment must include an injectableaminoglycoside and regular microbial sputum testing to monitor treatment progress. Patients with MDR-TB should be kept in negative pressure rooms to prevent cross infection.7 By Naz Ahmed, Wallaa Ali, RohanChitkara, Chris Davis, Sophie Harris and Yousuf Hussain Introduction Tuberculosis (TB) is an infectious disease caused by Mycobacteriumtuberculosis. In the UK in 2010, a total of 8,483 cases of tuberculosis were reported, of which 53% were pulmonary TB.1Transmission of TB occurs via droplet infection, for example when an infected person coughs or sneezes, and normally involves close contact with an untreated, infected person over a prolonged period of time. Other risk factors include being HIV positive, immunocompromised or coming from an ethnic minority such as sub-Saharan Africa or South Asia. The rate of transmission is also increased in homeless patients, drug abusers, alcoholics and those who live in poverty or overcrowded housing. However, pulmonary TB is largely treatable by a drug regime of antibiotics for at least 6 months. Prevention Primary prevention of Pulmonary TB in the UK is through the Bacillus Calmette-Guérin (BCG) vaccine, which contains a live attenuated strain of Mycobacterium bovis. Since 2005, a compulsory nationwide programme has not been recommended and current protocol immunises children if they belong to the following high-risk categories6: Figure 2. First line pharmacological management.8 Figure 3. Second line pharmacological management.7,8 • Multi-Drug Resistant TB (MDR-TB) • This strain impedes the two most potent first line drugs. The reasons for drug resistance are6: • Non-adherence to treatment • Inaccurate prescriptions • Poor quality of drugs • Unreliable drug supply • Latent TB Treatment • Latent TB treatment prevents the risk of TB infection progressing into active TB. It is considered for people aged between 16-35 without HIV, a healthcare worker or any HIV positive patient who tests positive for latent TB. The two recommended regimens are6: • 6 months of Isoniazid, or • 3 month combined treatment of isoniazid and rifampicin, dependent on the age and HIV status of a patient. Pathophysiology Children living in areas with a high incidence of TB or born into a family infected with TB in the past 5 years. The pathophysiological sequence of events that develops in a previously unexposed person who is immunocompetant, is dependant on the interplay between Mycobacteriumtuberculosis and the host’s immunological response.3This is shown in Figure 1 below. Primary Tuberculosis 0-3 weeks Children with a parent/grandparent who was born in a country with a high incidence of TB. Unrestrained bacterial proliferation Alveolar macrophage activity >3 weeks Unvaccinated immigrants under the age of 16 from countries with a high incidence of TB. Figure 4. Mycobacterium tuberculosis 9 TH1 Cell Interferon gamma Mycobacterium tuberculosis Lungs infected Individuals with a high risk of occupational or travel exposure. Lysosome formation Diagnosis & Investigations The vaccine is 70-80% effective against the most severe forms of TB, however, there is little evidence that the vaccine is effective in those over the age of 16.11 Activated epithelioid / Langhans cells Bactericidal destruction A derivative of Mycobacterium Tuberculosis is injected into the patient and the development and inflammation is monitored. There are many different ways to reach a diagnosis of pulmonary TB. The most definitive is to grow a culture using the patient’s sputum, however, this can take between 2-12 weeks. Figure 6 shows the additional methods of making a faster diagnosis. Mantoux test Increased nitric oxide • Primary Tuberculosis • Subclinical presentation (common) • Wheeze, cough • Delayed-hypersensitivity reaction-associated with a small pleural effusion or erythemanodosum5 • Ranke Complex10/ 'Ghon Focus’ Fresh blood samples are mixed with antigens and tested for interferon gamma which may have been released by infected white blood cells. • Post-Primary5Tuberculosis • Fever, weight loss, tiredness, recurrent colds, night sweats • Cough, haemoptysis, purulent sputum • Upper lobe consolidation, apical cavitation, loss of volume • Pleural effusion/pneumonia Interferon gamma test Healed lesion Antimicrobial immunity An X-ray can show patchy or nodular shadows, loss of volume, and fibrosis with or without cavitation. It may also show calicification. PA X-ray Conclusion Caseatinggranuloma ‘Ghon focus’ Primary progressive tuberculosis A sputum sample is cultured to determine the presence of the bacillus. Further cultures are used to test the efficacy of antibiotics to the bacillus. Culture & Microscopy In conclusion, the rate of TB in the UK has increased over the past 15 years and it is now the only Western European nation with rising incidence levels12. This is mainly due to a rising prevalence of a non-UK born population. TB remains a well-managed disease, providing the appropriate course of antibiotics is followed. However, failure to adhere to treatment can lead to drug resistance. This can be aided by the use of Directly Observed Therapies (DOT). The emergence of extremely-drug-resistant TB (XDR-TB) presents a further complication and highlights the need to promote the use of the International Standards for Tuberculosis Care (ITSC) to reduce resistance7. Hypersensitivity reaction Latent tuberculosis AuraminPhynol fluorescent stain A histological stain used to identify Tuberculosis Mycobacteria • Primary Progressive4Tuberculosis • Lower and middle lobe consolidation • Hilarlymphadenopathy • Pleural effusion • Lung cavitation (rare) To confirm the diagnosis a biopsy of the pleura, lymph nodes and solid lesions within the lung may be needed. Biopsy Reactivation/Reinfection Post-primary tuberculosis Progressive tissue damage with cavitation Figure 1. A flow chart showing the pathological sequence of events in pulmonary TB.2,3,4,5 Figure 6. The methods of diagnosing pulmonary TB.5,6 Figure 5. The typical clinical and pathological manifestations of pulmonary TB. 4,5,10 References Pedrazzoli D, Kruijshaar M, Anderson L, Abubakar I. Tuberculosis in the UK:2011 report. London: Health Protection Agency, December 2011. 2)Pinheiro M, Lucio M, Lima J LFC, Reis S. Liposomes as Drug Delivery Systems of TB: TB Etiology and Physiopathology. Available from: www.medscape.com/viewarticle/752329_2 (Accessed on 20th March 2012). 3) Schluger N W.The Pathogenesis of Tuberculosis.American Journal of Respiratory Cell and Molecular Biology. 2005. Vol.32. p252 4) Kumar V, Abbas AB, Fausto N, Aster JC. Robbins and Cotran Physiological Basis of Disease. 8thed, pp 367-371. Saunders Elsiver 2010. 5) Kumar P, Clark M. Kumar and Clark’s Clinical Medicine 7th Ed, pp864-865. Saunders Elsevier 2009. 6) National Institute for Health and Clinical Excellence. Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. Available from: http://www.nice.org.uk/nicemedia/live/13422/53638/53638.pdf (Accessed on 22nd March 2012) 7) Guidelines for the programmatic management of drug-resistant tuberculosis. Available from: http://whqlibdoc.who.int/publications/2011/9789241501583_eng.pdf (Accessed on 21st March 2012) 8) Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Rang and Dale’s Pharmacology. 7thed, pp 622-637. Saunders Elsevier. London 2012. 9) Todar’s Online Textbook of Bacteriology. Available from: http://textbookofbacteriology.net/MTBCDC.jpg. (Accessed on 24th April 2012) 10) Swansea Radiology Teaching Site. Available from: http://www.swansea-radiology.co.uk/case 35_results.html. (Accessed on 21st March 2012). 11) Patient UK ‘BCG Vaccine’. Available from: http://www.patient.co.uk/doctor/BCG-Vaccination.htm. (Accessed on 22nd March 2012). 12) NHS Choices ‘TB rises in UK and London’. Available from: www.nhs.uk/news/2010/12December/Pages/tb-tuberculosis-cases-rise-london-uk.aspx. Accessed on 21st March 2012). Faculty of Life Sciences www.manchester.ac.uk/lifesciences