Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control in Scotland

5 Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control in Scotland Health Protection Network Scottish Guidance Adapted from NICE guidelines for Scottish use March 2009

The Health Protection Network (HPN) is a network of existing professional organisations and networks in the health protection community across Scotland. It aims to promote, sustain, and coordinate good practice. The HPN supports a systematic approach to development, appraisal and adaptation of guidelines, seeking excellence in health protection practice. Supported by Health Protection Scotland Health Protection Scotland (HPS) is a non-profit, public sector organisation which is part of the Scottish National Health Service. It is dedicated to the protection of the public s health. Health Protection Network site: http://www.hps.scot.nhs.uk/about/hpn.aspx Citation for this document Health Protection Network. Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control in Scotland. Health Protection Network Scottish Guidance 5. Health Protection Scotland, Glasgow, 2008. Published by Health Protection Scotland, Clifton House, Clifton Place, Glasgow G3 7LN. Health Protection Scotland is a division of NHS National Services Scotland. First published March 2009 Health Protection Network 2009 The Health Protection Network has made every effort to trace holders of copyright in original material and to seek permission for its use in this document and the associated quick reference guide. Should copyrighted material have been inadvertently used without appropriate attribution or permission, the copyright holders are asked to contact the Health Protection Network so that suitable acknowledgement can be made at the first opportunity. Health Protection Network consents to the photocopying of this document for the purpose of implementation in NHSScotland. All other proposals for reproduction of large extracts should be addressed to: Health Protection Network Health Protection Scotland 1 Cadogan Square Cadogan Street Glasgow G2 7HF Tel: +44 (0) 141 300 1100 Email: hpsenquiries@hps.scot.nhs.uk Designed and typeset by: Graphics Team, Health Protection Scotland

Table of Contents Foreword i List of abbreviations ii Introduction 1 Patient-centred care 2 Key priorities for implementation 3 Management of active TB 3 Improving adherence 4 New entrant screening 4 BCG vaccination 4 Definitions used in this guideline 5 1 Guidance 8 1.1 Diagnosis 8 1.1.1 Diagnosing latent TB 8 1.1.2 Diagnosing active TB 9 1.2 Management of respiratory TB 13 1.2.1 Drug treatment 13 1.2.2 Infection control 14 1.3 Management of non-respiratory TB 17 1.3.1 Meningeal TB 17 1.3.2 Peripheral lymph node TB 18 1.3.3 Bone and joint TB: drug treatment 18 1.3.4 Bone and joint TB: routine therapeutic surgery 19 1.3.5 Pericardial TB 19 1.3.6 Disseminated (including miliary) TB 19 1.3.7 Other sites of infection 20 1.4 Monitoring, adherence and treatment completion 21 1.4.1 Treatment completion and follow-up 21 1.4.2 Improving adherence: directly observed therapy 21 1.4.3 Other strategies to improve adherence 22

1.5 Risk assessment and infection control in drug-resistant TB 23 1.5.1 Risk factors 23 1.5.2 Referral 24 1.5.3 Infection control 24 1.5.4 Treatment of non-mdr drug resistant TB 26 1.6 Management of latent TB 26 1.6.1 Treatment of latent TB infection 26 1.7 BCG vaccination 31 1.7.2 BCG vaccination for neonates 31 1.7.3 BCG vaccination for infants and older children 32 1.7.4 BCG vaccination for new entrants from high-incidence areas 33 1.7.5 BCG vaccination for healthcare workers 33 1.7.6 BCG vaccination for contacts of people with active TB 34 1.7.7 BCG vaccination for other groups 34 1.8 Contact Tracing 35 1.8.1 Contact tracing: human to human transmission 35 1.8.2 Contact tracing: cases on aircraft 37 1.8.3 Contact tracing: cases in schools 38 1.8.4 Contact tracing: community childcare 39 1.8.5 Contact tracing: cases in hospital inpatients and care home settings 39 1.8.6 New entrants from a high incidence country 40 1.8.7 Street homeless 42 1.8.8 Contact tracing in higher education settings 43 1.8.9 Contact tracing: cattle to human transmission 43 1.9 Preventing infection in specific settings 43 1.9.1 Healthcare environments: new NHS employees 43 1.9.2 Healthcare environments: occupational health 45 1.9.3 Prisons and remand centres 46 1.9.4 Social care (for example care homes/residential homes/domiciliary care): 47 2 Notes on the scope of the guidance 48 3 Implementation in the NHS 48

4 Research recommendations 49 4.1 Interferon-gamma tests 49 4.2 Directly observed therapy 50 4.3 New entrant screening and treatment for latent TB infection 50 4.4 Protective effects of BCG 50 4.5 Quality of life 51 4.6 Contact tracing in household contacts and homeless people 51 4.7 Incentives for attending new entrant screening 51 4.8 Incentives for homeless people attending chest X-ray screening 52 5 Review date 52 Appendix A: Grading scheme 53 Appendix B: Guideline development 56 Appendix C: The guideline review panel 58 Appendix D: Technical detail on the criteria for audit 59 Appendix E: The algorithms 61

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Foreword Tuberculosis (TB) is an age old problem. In Scotland, there were great advances in managing TB during the last century. Scotland s pioneering successes in TB control included addressing poor social conditions, encouraging screening and introducing antibiotic treatments. These measures resulted in dramatic reductions in the number of Scots living with active tuberculosis, leading to optimism that the problems of TB were largely a thing of the past. During the past decade, Scotland has seen a decline to a steady level of TB cases of around 350-400 cases per year, which compares very favourably with figures 10 or 100 times greater, which were seen in the 1940 s and the 1900 s respectively. However, in more recent years, TB has provided new challenges for public health. Sadly, the re-emergence of TB as a global public health threat has gone hand in hand with the global spread of HIV infection. At the same time we have witnessed the global emergence of multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB). Together, these issues have generated large increases in the numbers of new cases of TB in Sub-Saharan Africa, Asia and more recently, caused problems in parts of Europe. In response to these global challenges Health Protection Scotland has undertaken detailed surveillance to monitor TB in the Scottish population. Unlike the situation in England, Scotland has enjoyed a period over the last decade of relative stability in cases recorded (around 350-400 cases per year). However this period has seen a changing pattern of disease in which the number of TB cases who are thought to have acquired their infection out with the UK has increased each year. This pattern has seen us moving closer to the situation seen in England where the majority diagnosed with TB are born abroad or have likely acquired their infection abroad during prolonged travel in areas with a high burden of TB. Provisional figures for new cases diagnosed in Scotland in 2008 (approximately 450 cases) indicate that our case numbers cases are now increasing. Action is now needed in Scotland to reduce our TB numbers, whilst at the same time contributing to the international control of TB. The production of the Guideline Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control in Scotland represents the first step in the development of a Scottish Action Plan to tackle the problems of TB and to reduce the burden of this disease in Scotland. This document is adapted from the NICE TB Guidelines which were issued in 2006 for use in England. They have been developed for use in Scotland using the AGREE instrument. Importantly, these Scottish TB Guidelines contain useful practical suggestions and best practice points as well as suggesting areas for research and development for the future. Dr Harry Burns Chief Medical Officer i

List of abbreviations BCG BNF BNF-C CNS CPHM CT DOT HIV HPS IMT MDR MRI MTB NHS NICE PAG SHTM TB XDR Bacille Calmette-Guérin British National Formulary British National Formulary for children Central Nervous System Consultant in Public Health Medicine Computed Tomography Directly Observed Therapy Human Immunodeficiency Virus Health Protection Scotland Incident Management Team Multi-Drug Resistant Magnetic Resonance Imaging Mycobacterium tuberculosis National Health Service National Institute for Clinical Excellence Problem Assessment Group Scottish Technical Health Memorandum Tuberculosis Extensively Drug Resistant ii

Introduction The incidence of tuberculosis (TB) is influenced by risk factors such as exposure to, and susceptibility to, TB and levels of deprivation (poverty, housing, nutrition and access to healthcare), and differs in different parts of the United Kingdom. Where scientific evidence supports it, this guideline makes recommendations on service organisation, as well as for individual teams of healthcare professionals. The guideline aims to focus NHS resources where they will combat the spread of TB, and some sections deal with high- and low-incidence areas separately. The guideline was designed for use in the National Health Service in England and Wales and adapted for use in Scotland. Readers in other countries, particularly where the incidence of TB is higher, should exercise caution before applying the recommendations. The guideline has introduced resource issues, audit points and research recommendations. Resource issues are areas that the guideline group felt were important in the clinical diagnosis or management of tuberculosis but has implications on current NHS resources. Audit points are areas that have timescales and are an opportunity to measure action in these areas over time. The Scottish TB guideline group endorses the original NICE research recommendations with the addition of using molecular typing techniques to translate epidemiological information into action. Scottish amendments within this document are shown in italicised blue text with a Saltire flag in the margin.

Patient-centred care This guideline offers best practice advice on the care of people with, or at risk of contracting, TB. Treatment and care should take into account patients individual needs and preferences. People with, or at risk of contracting, TB should have the opportunity to make informed decisions about their care and treatment. If patients do not have the capacity to make decisions, healthcare professionals should follow the Department of Health guidelines Reference guide to consent for examination or treatment (2001) (available from http://www.dh.gov.uk). From April 2007 healthcare professionals need to follow a code of practice accompanying the Adults with Incapacity (Scotland) Act 2000 (http://www.opsi.gov.uk/si/ si2005/20051790.htm). Good communication between healthcare professionals and patients is essential. It should be supported by the provision of evidence-based information offered in a form that is tailored to the needs of the individual patient. The treatment, care and information provided should be culturally appropriate and in a form that is accessible to people who have additional needs, such as people with physical, cognitive or sensory disabilities, and people who do not speak or read English. Unless specifically excluded by the patient, carers and relatives should have the opportunity to be involved in decisions about the patient s care and treatment. Carers and relatives should also be provided with the information and support they need. 2

Key priorities for implementation The following recommendations have been identified as priorities for implementation. Management of active TB A 6-month, four-drug initial regimen (6 months of isoniazid and rifampicin supplemented in the first 2 months with pyrazinamide and ethambutol) should be used to treat active respiratory TB I in: adults not known to be HIV-positive adults who are HIV-positive children. This regimen is referred to as standard recommended regimen in this guideline. Patients with active meningeal TB should be offered: a treatment regimen, initially lasting for 12 months, comprising isoniazid, pyrazinamide, rifampicin and a fourth drug (for example, ethambutol) for the first 2 months, followed by isoniazid and rifampicin for the rest of the treatment period a glucocorticoid at the normal dose range adults - equivalent to prednisolone 20-40 mg if on rifampicin, otherwise 10-20 mg children - equivalent to prednisolone 1-2 mg/kg, maximum 40 mg with gradual withdrawal II of the glucocorticoid considered, starting within 2 3 weeks of initiation. I II TB affecting the lungs, pleural cavity, mediastinal lymph nodes or larynx. In adults initiation steroids should be continued for two months followed by a gradually reduced dose over the following two months. Children may tolerate a more rapid tail off. 3

Improving adherence All patients should have a risk assessment for adherence to treatment (see appendix C, VIII). Use of directly observed therapy (DOT) is not usually necessary in the management of most cases of active TB. DOT should be considered for patients who have adverse factors on their risk assessment, in particular: street- or shelter-dwelling homeless people with active TB patients who misuse alcohol patients and or families with likely poor adherence, in particular those who have a history of non-adherence The TB service should tell each person with TB who their named key worker is, and how to contact them. This key worker should facilitate education and involvement of the person with TB in achieving adherence. New entrant screening New entrants I should be identified for TB screening from the following information: Port of Arrival reports new registrations with primary care entry to education (including universities) links with statutory and voluntary groups working with new entrants. BCG vaccination Neonatal BCG vaccination for any baby at increased risk of TB should be discussed with the parents or legal guardian. In Scotland any baby at an increased risk of TB should be offered a BCG following discussion with parents and consent from parents or legal guardian. NHS areas with a high incidence of TB II should consider vaccinating all neonates soon after birth (currently none in Scotland). I II New entrants are defined as people who have recently arrived in or returned to the UK from highincidence countries, with an incidence of more than 40 per 100,000 per year, as listed by the Health Protection Agency (go to http://www.hpa.org.uk and search for WHO country data TB ). Incidence of more than 40 per 100,000 (listed by the Health Protection Agency as above) 4

Definitions used in this guideline Active TB when a person is currently unwell with TB disease. Aerosol generating procedure an intervention or procedure which results in a fine droplet spray of extremely small (approx 0.001mm in diameter) respiratory secretions in the air. Aerosol generating procedures include bronchoscopy, chest physiotherapy, intubation, nasopharyngeal aspiration, nebulised therapies that result in increased respiratory secretions, sputum generating procedures (e.g. sputum induction), suctioning material from the respiratory tract, tracheostomy care and any procedure which induces a cough response I. Contacts can be defined as close contacts or casual contacts. Close contacts may include a boyfriend or girlfriend and visitors to the home of the index case with eight hours cumulative exposure, in addition to household contacts. Casual contacts may include work colleagues. Directly Observed Therapy (DOT) People with TB can be given treatment to take under direct observation by a healthcare professional or other suitable person where swallowing of the medication is observed. Drug resistance is defined as resistance to one or more anti-tb drug at the start of treatment. This includes multi-drug resistance (MDR) and extensively drug resistance (XDR). MDR is resistance to at least isoniazid and rifampicin. XDR is resistance to isoniazid AND rifampicin AND resistance to a fluoroquinolone AND resistance to one of more of the following injectable drugs: amikacin, capreomycin or kanamycin. High-incidence NHS area An NHS area with more than 40 cases of TB per 100,000 population per year. II Household contacts People sharing a bedroom, kitchen, bathroom or sitting room with the index case. Immunocompromised describes patients in whom the immune response is reduced or defective due to immunosuppression (for example HIV positive individuals, organ transplant recipients, those with malignancy or receiving chemotherapy). Such patients are vulnerable to opportunistic infections. Inform and advise information and advice on the risks and symptoms of TB, usually given in a standard letter. I II This list is not definitive and new procedures may be introduced which also generate aerosols. High-incidence country A country with more than 40 cases per 100,000 per year; these are listed by the Health Protection Agency go to http://www.hpa.org.uk and search for WHO country data TB 5

Key Worker is a named healthcare worker responsible for overseeing the care and management of a person with TB. Latent TB when a person is infected with TB but showing no signs or symptoms of TB disease. MTB Complex includes isolates identified as M. tuberculosis, M. bovis, M. africanum, M. microti or M. canettii. New entrants People who have recently arrived in or returned to the UK from highincidence countries having lived there for three months or more. Non Respiratory TB TB affecting areas other then the lungs, pleural cavity, mediastinal lymph nodes or larynx. Rapid liquid methods fast laboratory tests confirming TB from a liquid culture. Rapid molecular diagnostic tests fast laboratory tests confirming TB using molecular techniques. Respiratory TB I TB affecting the lungs, pleural cavity, mediastinal lymph nodes or larynx. Solid Methods traditional laboratory tests used to confirm TB by solid culture techniques. Sputum negatives are cases with three negative sputum samples taken on three separate days. Sputum samples should be spontaneously produced sputum (or induced sputum if this is not possible) taken on three separate days, ideally early morning. If these are not available, three early morning gastric lavage or bronchoscopy samples should be obtained. Gastric lavage samples should be obtained ideally on three separate days, however the bronchoscopy samples may be taken from a single bronchoscopy session. Susceptible patient is defined as a patient thought to be at risk of contracting tuberculosis. Standard recommended regimen The 6-month, four-drug initial regimen of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampicin. I The WHO classification for a pulmonary TB case is a patient with TB of the lung parenchyma or the tracheobroncial tree (including larynx). An extra-pulmonary TB case is a patient with TB of organs other than the lungs or tracheobronchial tree. A patient with both pulmonary and extra-pulmonary TB is classified as pulmonary.

Drug regimen abbreviations for TB treatment Drug regimens are often abbreviated to the number of months a phase of treatment lasts, followed by letters for the drugs administered in that phase: H is isoniazid, R rifampicin, Z pyrazinamide, E ethambutol, S streptomycin For example: 2HRZE/4HR is the standard recommended regimen. 2HRE/7HR is 2 months of isoniazid, rifampicin and ethambutol followed by 7 months of isoniazid and rifampicin. 7

The following guidance is evidence based. Appendix A shows the grading scheme used for the recommendations: A, B, C, D or good practice point ; recommendations on diagnostic tests are graded A(DS), B(DS), C(DS) or D(DS). A summary of the evidence on which the guidance is based is provided in the full original NICE guideline. 1 Guidance 1.1 Diagnosis 1.1.1 Diagnosing latent TB Evidence is emerging on the performance of interferon-gamma tests. If this new evidence is significant, the guideline group will consider updating the guideline. 1.1.1.1 To diagnose latent TB: D Mantoux testing should be performed in line with the Green Book I (Evidence issue) those with positive results (or in whom Mantoux testing may be less reliable) should then be considered for interferon-gamma immunological testing, if available. if testing is inconclusive, the person should be referred to a TB specialist (see section 1.6 for management of latent TB). I In this guideline the Green Book is the 2006 edition of Immunisation against infectious disease, published by the Department of Health. Available from http://www.dh.gov.uk/policyandguidance/ HealthAndSocialCareTopics/GreenBook/fs/en); a printed version was published during 2006. The Green Book contains details of at risk groups who may have suppressed responses to tuberculin skin testing. 8

1.1.2 Diagnosing active TB 1.1.2.1 To diagnose active respiratory TB: a posterior anterior chest X-ray should be taken; chest X-ray appearances suggestive of TB should lead to further diagnostic investigation C(DS) multiple sputum samples should be sent for TB microscopy and culture for suspected respiratory TB before starting treatment if possible or, failing that, within 7 days of starting. C(DS) Sputum samples should ideally but not necessarily be three early morning samples spontaneously produced sputum should be obtained if possible; otherwise induction of sputum or bronchoscopy and lavage should be used B(DS) in children unable to expectorate sputum, induction of sputum should be considered if it can be done safely, with gastric washings considered as third line B(DS) if there are clinical signs and symptoms consistent with a diagnosis of TB, treatment should be started without waiting for culture results (see section 1.2.1 for details) the standard recommended regimen should be continued in patients whose subsequent culture results are negative unless treatment is contra-indicated or an alternative diagnosis has been made autopsy samples should be sent for TB microscopy and culture in a dry sterile container (and not placed in formalin) if TB is a possibility. 9

1.1.2.2 To diagnose active non-respiratory TB: advantages and disadvantages of both biopsy and needle aspiration should be discussed with the patient, with the aim of obtaining adequate material for diagnosis B(DS) if non-respiratory TB is a possibility, part or all of any of the following samples should be placed in a dry sterile container (and not all placed in formalin) and sent for TB microscopy and culture: (Resource Issue) lymph node biopsy pus aspirated from lymph nodes pleural biopsy any radiological sample sent for routine culture microbiology staff should routinely perform TB culture on the above samples (even if it is not requested) microbiology staff should have a low threshold for performing culture on the following samples even when not specifically requested: histology samples aspiration samples autopsy samples the appropriate treatment regimen should be started without waiting for culture results if the histology and clinical picture are consistent with a diagnosis of TB (see sections 1.2 and 1.3) all patients with non-respiratory TB should have a chest X-ray to exclude or confirm coexisting respiratory TB; in addition, tests as described in table 1 should be considered the appropriate drug regimen (see sections 1.2 and 1.3) should be continued even if subsequent culture results are negative but where TB is still clinically suspected. C(DS) 10

Table 1: Suggested site-specific investigations in the diagnosis and assessment of TB Site Imaging Biopsy Microscopy/Culture Lymph node Node1 Node or aspirate Bone/joint Plain X-ray and computed tomography (CT) Magnetic resonance imaging (MRI) Site of disease Biopsy or paraspinal abscess Site or joint fluid Gastrointestinal Ultrasound Omentum Biopsy CT abdomen Bowel Ascites Genitourinary Intravenous urography Site of disease Early morning urine Ultrasound Site of disease CT (kidney, ureter, bladder) Endometrial curettings Disseminated Chest X-ray Lung Bronchial wash CT (chest and abdomen) Liver Bone marrow Liver Bone marrow Blood CSF Central nervous system CT brain Tuberculoma Cerebrospinal fluid MRI Skin Site of disease Site of disease Pericardium Echocardiogram Pericardium Pericardial fluid Cold/liver abscess Ultrasound Site of disease Site of disease Lung Posterior-anterior chest X-ray Possible CT Thorax Sputum Bronchial washing NG aspirate Gastric lavage Pleural cavity Posterior-anterior chest X-ray Ultrasound Pleural biopsy Pleural fluid Pleural biopsy Possible CT Thorax Mediastinal lymph nodes Posterior-anterior chest X-ray Mediastinal biopsy Mediastinal biopsy CT chest Larynx Posterior-anterior chest X-ray Laryngeal biopsy Laryngeal biopsy CT Neck and chest 11

1.1.2.3 Rapid molecular diagnostic tests for Mycobacterium tuberculosis complex (M tuberculosis, M bovis, M africanum, M microti and M canetti) on primary specimens should be used providing the following conditions are met: ( resource issue) rapid confirmation of a TB diagnosis in a sputum smearpositive person would alter their care, or before conducting a large contact-tracing initiative. In the event of uncertainty the Scottish Mycobacteria Reference laboratory should be contacted for further advice I. 1.1.2.4 Clinicians should still consider a diagnosis of non-respiratory TB if rapid diagnostic tests are negative, for example in pleural fluid, cerebrospinal fluid and urine. B(DS) 1.1.2.5 Clinical signs and other laboratory findings consistent with TB meningitis should lead to treatment (see section 1.3.1), even if a rapid diagnostic test is negative, because the potential consequences for the patient are severe. 1.1.2.6 Before conducting a large contact-tracing initiative (for example, in a school or hospital), the species of mycobacterium should be confirmed to be MTB complex by rapid diagnostic tests on microscopy- or culture-positive material. Clinical judgement should be used if tests are inconclusive or delayed. 1.1.2.7 If a risk assessment suggests a patient has multi drug resistant (MDR) TB or extensively drug resistant (XDR) TB (see section 1.5.1): rapid diagnostic tests should be conducted for rifampicin and isoniazid resistance infection control measures and treatment for MDR TB should be started as described in section 1.5, pending the result of the tests. 1.1.2.8 Rapid diagnostic tests for MTB complex identification may be conducted on biopsy material where the sample has been inappropriately placed in formalin and histology is consistent with mycobacterial infection. I Scottish Mycobacteria Reference Laboratory, Royal Infirmary of Edinburgh, Little France, Edinburgh, EH16 4SA. Tel : 0131 242 6016, Fax: 0131 242 6008 12

1.1.2.9 Clinical samples should ideally be sent for culture by automated liquid methods in addition to solid methods, bearing in mind that laboratories need a certain level of throughput to maintain quality control. (resource issue) 1.2 Management of respiratory TB Respiratory TB is defined as active TB that is affecting any of the following: lungs pleural cavity mediastinal lymph nodes larynx. 1.2.1 Drug treatment 1.2.1.1 Once a diagnosis of active TB is made, the clinician responsible for care should refer the person with TB to a physician with training in, and experience of, the specialised care of people with TB. TB in children should be managed either by a paediatrician with experience and training in the treatment of TB, or by a general paediatrician with advice from a specialised physician. If these arrangements are not possible, advice should be sought from more specialised colleagues throughout the treatment period. C The TB service for adults and children should include specialised TB nurses and health visitors 1.2.1.2 A daily 6-month, four-drug initial regimen (6 months of isoniazid and rifampicin supplemented in the first 2 months with pyrazinamide and ethambutol) should be used to treat active respiratory TB in: adults not known to be HIV-positive A adults who are HIV-positive B children. B This regimen is referred to as standard recommended regimen in this guideline and is outlined in the current British National Formulary (BNF) or BNF for children (BNF-C) (http://www.bnf. org/bnf/ and http://bnfc.org/bnfc/). 13

1.2.1.3 Where possible, fixed-dose combination tablets should be used as part of any TB treatment regimen. C 1.2.1.4 There are two main approaches for administering the regimen, either daily or thrice weekly dosing. The doses for each approach are different and are listed in the current BNF and BNF-C. 1.2.1.5 A daily or thrice-weekly dosing regimen (using the dosages given in BNF and BNF-C) should be considered for patients receiving directly observed therapy (DOT) (see section 1.4.2). 1.2.1.5 A twice-weekly dosing regimen should not be used for the treatment of active TB. 1.2.2 Infection control Engineering controls are important to prevent TB transmission in hospitals. NHS boards that care for patients with or suspected of having TB should have the appropriate facilities in which to care for them. In recognition of the challenges posed by MDR TB for infection control, there should be an adequate arrangements for provision of suitable negative-pressure rooms for all NHS board areas for treating respiratory (and suspected respiratory) TB (resource issue). The recommendations below deal with the levels of isolation for infection control in hospital settings: negative-pressure rooms, which have air pressure continuously or automatically measured, as defined by NHS Health Facilities Scotland in SHTM 2025 I single rooms that are not negative pressure but are vented to the outside of the building A member of the hospital infection control team and/or physicians should carry out a risk assessment on each patient. This risk assessment should include the engineering controls. Rooms where TB patients are nursed and aerosol generating procedures performed should form the basis of a facilities needs assessment. I Scottish Health Technical Memorandum 2025 Ventilation in healthcare premises (available from http:// www.hfs.scot.nhs.uk/publications/view-category.php?sec=1&cat=27) 14

1.2.2.1 All patients with proven or suspected TB should have risk assessments for multi drug resistance (see section 1.5) and for HIV immediately on admission. Based on this risk assessment, a decision should be made with regard to their placement in a cubicle with negative pressure. This does not apply to transient patients residing in areas for less than eight hours. 1.2.2.2 Unless there is a clear clinical or socioeconomic need, such as children or homelessness, people with TB at any site of disease should not be admitted to hospital for diagnostic tests or for care. 1.2.2.3 If admitted to hospital, patients with suspected respiratory TB should be given a single room, preferably a negative-pressure room. The door should remain closed as much as possible. If a negative pressure cubicle is unavailable the infection control team should risk assess whether the patient is best served by management in a single room or transfer to another hospital with an available negative-pressure facility. Patients with proven or suspected MDR TB should always be admitted to a negative-pressure facility. 1.2.2.4 Patients with respiratory TB should be separated from immunocompromised patients, either by admission to a single room (negative pressure if available) on a separate ward, or to a negative-pressure room on the same ward or undergo isolation in a single room. 1.2.2.5 Any visitors to a child with TB in hospital should be screened as part of contact tracing (as covered in section 1.8.1.2), and kept separate from other patients until they have been excluded as the source of infection. 1.2.2.6 There is an increasing prevalence of HIV positive patients in general medicine wards in hospital, many of whom remain undiagnosed. TB patients admitted to a setting where care is provided for HIV-positive or other immunocompromised patients should be considered infectious and should stay in a negative-pressure room until: For people who were sputum smear positive at admission: 1. the patient has had at least 2 weeks of appropriate multiple drug therapy, and 2. there is definite clinical improvement on treatment, for example remaining afebrile for at least 48 hours 15

3. if moving to accommodation (inpatient or home) with HIV positive or immunocompromised patients, the patient has had at least three negative microscopic smears on separate occasions over a 3-day period, and 4. the patient is showing tolerance to the prescribed treatment and an ability and agreement to adhere to treatment. Patients admitted to a care setting where there are no immunocompromised patients are considered infectious and must stay in a negative-pressure room until: the patient has had at least 2 weeks treatment and there is definite clinical improvement. For people who were sputum smear negative at admission; the infection risk to others is very small and as a result these patients can be nursed on an open ward (if no side room is available). 1.2.2.7 For settings where care is delivered to patients with or suspected to have TB, there should be a risk assessment carried out. This risk assessment should include an engineering assessment of anywhere where aerosol generating procedures are performed (for example bronchoscopy suites, outpatient clinics etc) which states that it is safe to do so. Aerosol generating procedures should not be carried out in an open ward setting when patients have or are suspected to have TB. 1.2.2.8 Healthcare workers caring for people with TB should wear FFP3 fit tested masks (see 1.5.3.2) and use standard infection control precautions when: MDR TB is suspected (see section 1.5.3.1) aerosol-generating procedures are being performed Intensive nursing intervention is required if the healthcare worker is likely to have close contact (equivalent to household contact) for a cumulative total for eight hours or more When such respiratory protection is used, the reason should be explained to the person with TB. The equipment should meet the standards of the Health and Safety Executive. See section 1.5.3 for further details of MDR TB infection control. 16

1.2.2.9 An increasing number of immunocompromised patients are being managed in hospital. Inpatients with smear-positive respiratory TB should be asked (with explanation) to wear a surgical mask whenever they leave their room until they have had 2 weeks drug treatment. This is to reduce the chance of exposure to immunocompromised patients. 1.3 Management of non-respiratory TB 1.3.1 Meningeal TB 1.3.1.1 Patients with active meningeal TB should be offered: a treatment regimen, initially lasting for 12 months, comprising isoniazid, pyrazinamide, rifampicin and a fourth drug (for example, ethambutol) for the first 2 months, followed by isoniazid and rifampicin for the rest of the treatment period a glucocorticoid at the normal dose range adults: equivalent to prednisolone 20-40 mg if on rifampicin, otherwise 10-20 mg I A (evidence issue) children: equivalent to prednisolone 1-2 mg/kg, maximum 40 mg with gradual withdrawal II of the glucocorticoid considered, starting within 2 3 weeks of initiation. 1.3.1.2 Clinicians prescribing treatment for active meningeal TB should consider as first choice: a daily dosing schedule B using combination tablets. D I Please note this differs from the previous guidance issued in 1998 II In adults, initiation steroids should be continued for two months followed by a gradually reduced dose over the following two months. However, children may tolerate a more rapid tail off of steroids. 17

1.3.2 Peripheral lymph node TB 1.3.2.1 For patients with active peripheral lymph node tuberculosis, the first choice of treatment should: be the standard recommended regimen (see section 1.2.1 for further details) B use a daily dosing schedule include combination tablets. B D 1.3.2.2 Patients with active peripheral lymph node TB who have had an affected gland surgically removed should still be treated with the standard recommended regimen. 1.3.2.3 Drug treatment of peripheral lymph node TB should normally be stopped after 6 months, regardless of the appearance of new nodes, residual nodes or sinuses draining during treatment. 1.3.3 Bone and joint TB: drug treatment 1.3.3.1 The standard recommended regimen (see section 1.2.1 for details) should be planned and started in people with: active spinal TB B active TB at other bone and joint sites. C 1.3.3.2 Clinicians prescribing treatment for active bone and joint tuberculosis should consider as first choice: a daily dosing schedule B using combination tablets. D 1.3.3.3 A computed tomography (CT) or magnetic resonance (MR) scan should be performed on patients with active spinal TB who have neurological signs or symptoms. If there is direct spinal cord involvement (for example, a spinal cord tuberculoma), management should be as for meningeal TB (see section 1.3.1). 18

1.3.4 Bone and joint TB: routine therapeutic surgery 1.3.4.1 In patients with spinal TB, anterior spinal fusion should not be performed routinely. B 1.3.4.2 In patients with spinal TB, anterior spinal fusion should be considered if there is spinal instability or evidence of spinal cord compression. 1.3.5 Pericardial TB 1.3.5.1 For patients with active pericardial TB, the first choice of treatment should: be the standard recommended regimen (see section 1.2.1 for details) B use a daily dosing schedule include combination tablets. B D 1.3.5.2 In addition to anti-tb treatment, patients with active pericardial TB should be offered: for adults, a glucocorticoid equivalent to prednisolone at 60 mg/day A for children, a glucocorticoid equivalent to prednisolone 1 mg/kg/day (maximum 40 mg/day) with gradual withdrawal I of the glucocorticoid considered, starting within 2 3 weeks of initiation. 1.3.6 Disseminated (including miliary) TB 1.3.6.2 For patients with disseminated (including miliary) TB, the first choice of treatment should: be the standard recommended regimen (see section 1.2.1 for details) B use a daily dosing schedule include combination tablets. B D I In adults, initiation steroids should be continued for 2 months followed by a gradually reduced dose over the following 2 months. However, children may tolerate a more rapid tail off of steroids. 19

1.3.6.2 Treatment of disseminated (including miliary) TB should be started even if initial liver function tests are abnormal. If the patient s liver function deteriorates significantly on drug treatment, advice on management options should be sought from clinicians with specialist experience of these circumstances. 1.3.6.3 Patients with disseminated (including miliary) TB should be tested for central nervous system (CNS) involvement by: brain scan (CT or MRI) and/or lumbar puncture for those with CNS signs or symptoms lumbar puncture for those without CNS signs and symptoms. If evidence of CNS involvement is detected, treatment should be the same as for meningeal TB (see section 1.3.1). 1.3.7 Other sites of infection 1.3.7.1 For patients with: active genitourinary TB, or active TB of any site other than: - respiratory system - CNS (typically meninges) - peripheral lymph nodes - bones and joints - pericardium - disseminated (including miliary) disease the first choice of treatment should: be the standard recommended regimen (see section 1.2.1 for details) B use a daily dosing schedule include combination tablets. B D 20

1.4 Monitoring, adherence and treatment completion 1.4.1 Treatment completion and follow-up 1.4.1.1 Follow-up clinic visits should not be conducted routinely after treatment completion D unless there are clinical concerns about a high risk of relapse or secondary complications. 1.4.1.2 Patients should be alerted to the risk and signs and symptoms of relapse and how to contact the TB service rapidly through primary care or a TB clinic. Key workers should ensure that patients at increased risk of relapse are particularly well informed about symptoms. 1.4.1.3 Patients who have had drug-resistant TB should be considered for follow-up for 12 months after completing treatment. Patients who have had MDR TB should be considered for prolonged follow-up with an annual review or assessment for 5 years. 1.4.2 Improving adherence: directly observed therapy 1.4.2.1 All patients should have a risk assessment for adherence to treatment (see appendix VIII), and DOT should be considered for patients who have adverse factors on their risk assessment, in particular: street- or shelter-dwelling homeless people with active TB B patients with likely poor adherence, in particular those who have a history of non-adherence. Use of directly observed therapy (DOT) is not usually necessary in the management of most cases of active TB. A 1.4.2.2 Clinicians who are planning to start a patient on a course of DOT should consider ways to mitigate the environmental, financial and psychosocial factors that may reduce adherence, including stability of accommodation and transport. The setting, observer and frequency of treatment should be arranged to be most practicable for the person with TB. The person with TB and his or her assigned key worker should be involved in deciding these arrangements. DOT should also be supported by frequent contact with the key worker (see 1.4.3.2). In appropriate circumstances, the key worker may transfer responsibility for certain tasks (e.g. administering drugs) to a member of the patients family or primary care team, for example a health visitor or district nurse. 21

1.4.3 Other strategies to improve adherence 1.4.3.1 To promote adherence, patients should be involved in treatment decisions at the outset of treatment for active or latent TB. The importance of adherence should be emphasised during discussion with the patient when agreeing the regimen. 1.4.3.2 The TB service should tell each person with TB who their named key worker is, and how to contact them. This key worker should facilitate education and involvement of the person with TB in achieving adherence. 1.4.3.3 TB services (and primary care services) should consider the following interventions to improve adherence to treatment for active or latent TB if a patient defaults: reminder letters in appropriate languages B health education counselling B patient-centred interview and health education booklet B home visits patient diary random urine tests and other monitoring (for example, pill counts) help or advice about where and how to get social security benefits, housing and social services. use an identified pharmacist to issue medication on a more frequent basis Centralised supplies of anti-tb drugs Combined care for other co-occurring conditions Prescriptions for TB medication were made free in Scotland from 1 October 2007 I I The NHS (Charges for Drugs and Appliances)(Scotland) (No.2) Regulations 2007 came into force on 1 October 2007 and provide the supply of medicines for the treatment of Tuberculosis to be supplied free of charge. 22

1.4.3.4 Pharmacies should make liquid preparations of anti-tb drugs readily available to TB patients who may need them for example, children and people with swallowing difficulties. 1.4.3.5 TB services should assess local language and other communication needs and, if there is a demonstrated need, provide patient information accordingly I. 1.5 Risk assessment and infection control in drugresistant TB 1.5.1 Risk factors 1.5.1.1 A risk assessment for drug resistance should be made for each patient with TB, based on the risk factors listed below: C 1. history of prior TB drug treatment; prior TB treatment failure 2. contact with a known case of drug-resistant TB 3. birth in a foreign country, particularly high-incidence countries II 4. HIV infection 5. residence in London or another area with a known prevalence of greater than 40 cases per 100,000 population 7. age profile, with highest rates between ages 25 and 44 8. male gender. 1.5.1.2 The TB service should consider the risk assessment for drug resistance and, if the risk is regarded as significant, urgent molecular tests for rifampicin resistance should be performed on smear-positive material or on positive cultures if appropriate. I II Patient information should be drawn from national high-quality resources if available; for examples, see http://www.hpa.org.uk. Information on TB will be added to the National Knowledge Service website (http://www.nks.nhs.uk) over the coming months. Countries with more than 40 cases per 100,000 per year, as listed by the Health Protection Agency (go to http://www.hpa.org.uk and search for WHO country data TB ). 23

1.5.1.3 Response to treatment should be closely monitored in patients at increased risk of drug resistance. If there is no clinical improvement within 2 months or if cultures remain positive after the 4th month of treatment ( treatment failure ), compliance issues or drug resistance should be suspected and treatment reviewed with a clinician experienced in the treatment of MDR TB. (See section 1.2.1 for details of the standard recommended regimen.) 1.5.2 Referral 1.5.2.1 The care of patients with MDR TB should be undertaken by a specialist I in MDR TB in conjunction with a microbiologist with expertise in TB. The views of the patient should be sought and taken into account, and shared care should be considered. 1.5.3 Infection control 1.5.3.1 Patients with suspected or known infectious MDR TB who are admitted to hospital should be admitted to a negativepressure room. If none is available locally, the patient should be transferred to a hospital that has these facilities and a clinician experienced in managing complex drug-resistant cases. Care should be carried out in the negative-pressure room until the patient is found to be non-infectious or non-resistant, and ideally until cultures are negative. Risk factors for MDR TB Risk factors for drug resistant TB (see section 1.5.1.1) A contact of MDR TB case Foreign born person from a country with a high incidence of MDR TB II (>10% of TB cases MDR TB). Travel or residence (3 months or more) in a country or setting with high incidence of MDR TB I II For a local list of specialists in MDR TB contact the local consultant in public health medicine. A UK wide virtual community of experts on MDR TB management is also available by contacting MDRTBservice@ctc. nhs.uk or 0151 600 142. Specialist expertise in the public health management of MDR-TB cases is available from Health Protection Scotland 0141 300 1100 Countries with a high incidence of MDR TB are available from the http://www.who.int and searching for MDR TB country data. The WHO 2008 MDR TB and XDR TB world report is available at http://www.who.int/ tb/challenges/mdr/mdrtbfacts_june08.pdf 24

1.5.3.2 Staff should wear FFP3 masks I during contact with a patient with suspected or known MDR TB while the patient is considered infectious. Wearers of FFP3 masks should undergo facepiece fit testing II before use to ensue that the mask fits correctly. The number of staff entering the isolation room during this time should be restricted to a minimum. Visitors to patients with known or suspected MDR TB should wear a mask. Where possible this should be a FFP3 mask and wearers should undergo facepiece fit testing. The number of visitors entering during this time should be restricted to a minimum. 1.5.3.3 Before the decision is made to discharge a patient with suspected or known MDR TB from hospital (i.e. patient demonstrated to be non-infectious by three negative smears, culture negative (most rapidly confirmed by liquid methods) and tolerating treatment), secure arrangements for the supervision and administration of all anti-tb therapy should have been agreed with the patient and carers. 1.5.3.4 The decision to discharge a patient with suspected or known MDR TB should be discussed with the infection control team, the local microbiologist, the local TB service, the consultant in public health medicine and other multidisciplinary agencies. Many patients with MDR TB have a history of poor compliance so a risk assessment for DOT should be carried out in these patients with an option for daily dosing. 1.5.3.5 Negative-pressure rooms used for infection control in MDR TB should meet the standards as defined by NHS Health Facilities Scotland III, and should be clearly identified for staff, for example by a standard sign. Such labelling should be kept up to date. For a summary of recommendations on infection control, see the algorithm on isolation decisions for patients with suspected respiratory TB (appendix E algorithm I). I II III European standard EN149:2001; masks should meet the standards in Respiratory protective equipment at work: a practical guide HSG53 published by the Health and Safety Executive (2005). Available from http://www.hsebooks.com/books Information on this can be accessed on the HPS website at http://www.documents.hps.scot.nhs.uk/hai/ infection-control/sicp/ppe/mic-p-ppe-2007-02.pdf Scottish Health Technical Memorandum 2025 Ventilation in healthcare premises (available from http:// www.hfs.scot.nhs.uk/guest/decontamination/cdver2/contents1.pdf) 25

1.5.4 Treatment of non-mdr drug resistant TB 1.5.4.1 Patients with drug resistant TB, other than MDR, should be under the care of a specialist physician with appropriate experience in managing such cases. First-choice drug treatment is set out in table 2. Table 2 Recommended regimens for non-mdr drug resistant TB Drug resistance Initial phase Continuation phase S 2RHZE 4RH H known before treatment 2RZSE 7RE found after starting treatment 2RZE 10RE Z 2RHE 7RH E 2RHZ 4RH R (only if confirmed isolated resistance) 2HZE 16HE S+H 2RZE 10RE Other individualised See definitions for details of abbreviations 1.6 Management of latent TB 1.6.1 Treatment of latent TB infection 1.6.1.1 Treatment of latent TB infection should be considered for people in the following groups, once active TB has been excluded by chest X ray and examination. People identified through screening (see section 1.8.1.2) who are: - younger than 36 years (because of increasing risk of hepatotoxicity with age) - any age with HIV - any age and a healthcare worker and are either: - Mantoux positive (6-14 mm), interferon gamma positive (if available) and without prior BCG vaccination, or - strongly Mantoux positive (15 mm or greater), interferon-gamma positive (if available), and with prior BCG vaccination. 26