National Guidelines on the Treatment of Tuberculosis Infection PDF 2023

 National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION TABLE OF CONTENTS PREFACE 1 ACKNOWLEDGEMENTS 2 LIST OF...

 National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION TABLE OF CONTENTS PREFACE 1 ACKNOWLEDGEMENTS 2 LIST OF ABBREVIATIONS 3 LIST OF DEFINITIONS 4 EXECUTIVE SUMMARY 5 1. INTRODUCTION AND RATIONALE 9 1.1 BACKGROUND 9 1.2 TB PREVENTIVE TREATMENT (TPT) 9 1.3 TESTS OF TB INFECTION: TUBERCULIN SKIN TESTS (TST) AND INTER- FERON-GAMMA RELEASE ASSAYS (IGRA) 10 2. PURPOSE OF THE GUIDELINES 12 3. ORGANISATION OF THE GUIDELINES 12 4. ADULT, ADOLESCENT AND OLDER CHILD CONTACTS 13 4.1 TPT SHOULD BE OFFERED TO: 13 4.2 TPT SHOULD BE DEFERRED OR NOT OFFERED IF THE INDIVIDUAL: 13 4.3 MANAGEMENT OF TPT IN ADULT, ADOLESCENT, AND OLDER CHILD (WEIGHING MORE THAN25 KILOGRAMS) CONTACTS 13 4.3.1 Evaluation for TB disease amongst adult, adolescent, and older child contacts 13 4.3.2 TPT regimens for adult, adolescent, and older child (≥25kg) contacts 14 5. CHILD CONTACTS: CHILDREN WEIGHING LESS THAN 25 KILOGRAMS AND INFANTS 16 5.1 TPT SHOULD BE OFFERED TO 16 5.2 TPT SHOULD BE DEFERRED OR NOT OFFERED IF THE CHILD: 16 5.3 MANAGEMENT OF TPT IN CHILDREN WEIGHING LESS THAN 25 KILOGRAMS 16 5.3.1 Evaluation of child contacts 16 5.3.2 TPT regimens for children weighing less than 25 kilograms 18 5.4 MANAGEMENT OF TPT IN CHILDREN LIVING WITH HIV (IRRESPECTIVE OF TB EXPOSURE) 19 5.5 MANAGEMENT OF TPT IN TB-EXPOSED NEWBORNS (BABIES BORN TO MOTHERS DIAGNOSED WITH PRE-NATAL OR PERI-PARTUM TB OR WITH OTHER SIGNIFICANT TB EXPOSURE) 19 6. TPT IN PREGNANT AND BREASTFEEDING WOMEN WITH TB EXPOSURE OR LIVING WITH HIV 21 6.1 TPT SHOULD BE OFFERED TO ALL PREGNANT AND BREASTFEEDING WOMEN (REGARDLESS OF THEIR HIV STATUS) WITH SIGNIFICANT TB EXPOSURE 21 i  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION 6.2 TPT SHOULD BE DEFERRED OR NOT OFFERED IF THE PREGNANT WOMAN: 21 6.3 MANAGEMENT OF TPT AMONGST HIVNEGATIVE AND HIV-POSITIVE PREGNANT AND BREASTFEEDING WOMEN WITH TB EXPOSURE 21 6.3.1 Evaluation for TB disease amongst pregnant and breastfeeding women 21 6.3.2 Considerations for TPT initiation in pregnant and breastfeeding women living with HIV: 22 6.3.3 TPT treatment options for pregnant and breastfeeding women 22 7. PEOPLE LIVING WITH HIV (PLHIV): ADULTS, ADOLESCENTS, AND CHILDREN IRRESPECTIVE OF AGE 23 7.1 WHO TPT SHOULD BE OFFERED TO 23 7.2 TPT SHOULD BE DEFERRED OR NOT OFFERED IF THE INDIVIDUAL LIVING WITH HIV: 23 7.3 MANAGEMENT OF TPT FOR PLHIV 23 7.3.1 Evaluation for TB disease amongst PLHIV 23 7.3.2 TPT regimens for PLHIV (adults, pregnant and breastfeeding women, adolescents, and children 25 kilograms or more) 24 7.3.3 TPT regimens for children weighing less than 25 kilograms living with HIV 24 8. SILICOSIS 26 8.1 WHO TPT SHOULD BE OFFERED TO 26 8.2 TPT SHOULD BE DEFERRED OR NOT OFFERED IF THE INDIVIDUAL: 26 8.3 MANAGEMENT OF TPT FOR PEOPLE WITH SILICOSIS 26 8.3.1 Evaluation for TB disease amongst silicosis 26 8.3.2 TPT regimens for adults with silicosis 26 9. OTHER HIGH-RISK GROUPS 27 10. PATIENT CATEGORISATION AND TREATMENT OUTCOMES 27 11. CLINICAL MONITORING OF PEOPLE ON TREATMENT 28 11.1 EDUCATION AND COUNSELLING OF ELIGIBLE INDIVIDUALS 28 11.2 FOLLOW-UP VISITS 28 11.3 ADVERSE EVENTS 28 11.4 DRUG-DRUG INTERACTIONS 30 11.5 TREATMENT INTERRUPTION AND DISCONTINUATION 30 12. MONITORING AND EVALUATION 32 ANNEXURES 34 ANNEXURE A: PHARMACOVIGILANCE FORM 35 ANNEXURE B: ADHERENCE PLAN 36 ANNEXURE C: TPT INTEGRATION INTO REPEAT PRESCRIPTION COLLECTION STRATEGIES FOR CLINICALLY STABLE PLHIV ON ART 38 ii  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION LIST OF FIGURES Figure 1. General algorithm for provision of TB preventive treatment using the Test and Treat Approach 10 Figure 2. Algorithm for provision of TB preventive treatment for adult, adolescent and older child (≥25kg) TB contacts 15 Figure 3. Algorithm for provision of TB preventive treatment for child contacts or children living with HIV 17 Figure 4. Algorithm for TB preventive treatment algorithm for TB-exposed newborns or infants 20 Figure 5. Algorithm for provision of TB preventive treatment for adults and adolescents living with HIV 25 Figure 6. Illustration of the data flow process from the facility to national level and reporting timeline 32 Figure 7. Illustration of a cascade for HIV-positive clients 33 Figure 8. Illustration of a cascade for contacts 33 LIST OF TABLES Table 1. Summary of TPT regimen options by patient type 11 Table 2. Patient categories and treatment outcomes 27 Table 3. Management of common adverse events 29 Table 4. Drug-drug interactions 30 Table 5. Management of individuals who miss doses of treatment 31 iii  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION PREFACE Dr. S. S. S. Buthelezi Director General: Health Tuberculosis (TB), HIV and AIDS are the major This guideline has been revised based on the causes of morbidity and mortality in the country. guidance provided by the World Health Organization Modelling work conducted showed that a combination (WHO), local evidence and experience with TB of interventions implemented at scale is required to preventive treatment (TPT) implementation. The reach the 2025 End TB Strategy targets of reducing purpose is to guide implementation, the management the TB incidence by 50 per cent and the TB mortality of patients started on TPT and the monitoring and by 75 per cent. It is for this reason that the following evaluation requirements. It is intended for clinicians, interventions were implemented: pharmacists and healthcare managers in the public and private sector. 1. prevention of new infections and TB disease I urge all healthcare workers to familiarise 2. early identification of people with TB through themselves with the content of this guideline and intensified and active TB detection strategies effectively implement the recommendations thereof 3. reduction in loss to follow-up to prevent TB disease in identified high risk groups. This intervention will reduce the burden of TB which 4. improvement of treatment outcomes continues to kill many people in the country and ensure that South Africans live long and healthy lives. Despite the increased uptake of Isoniazid Preventive Treatment (IPT) among people living with HIV and child contacts under five years of age, many eligible populations have still not received IPT, especially among people living with HIV. The COVID-19 pandemic has reversed the gains made in TB control due to severe disruption of TB screening, testing, and treatment services. More effort is therefore required to ensure that we mitigate DR S S S BUTHELEZI the losses incurred and catch up on progress against DIRECTOR GENERAL: HEALTH our targets. 1  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION ACKNOWLEDGEMENTS The development of these guidelines for TB preventive treatment took hard work by officials of the Department of Health, and representatives from partner organisations. Amongst many, we wish to acknowledge the contributions of the following: Members of the National TB Think Tank, especially the TB Prevention Task Team World Health Organization (WHO) United States (US) President’s Emergency Plan for AIDS Relief (PEPFAR) The Global Fund to Fight AIDS, TB and Malaria 2  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION LIST OF ABBREVIATIONS ART Antiretroviral treatment BCG Bacillus Calmette-Guérin CCMDD Central chronic medicine dispensing and distribution CHW Community health worker CLHIV Children living with HIV CXR Chest x-ray DHMIS District Health Management Information System DTG Dolutegravir DSD Differentiated service delivery DS-TB Drug-susceptible TB FDC Fixed-dose combinations HIV Human immunodeficiency virus HLM High level meeting IGRA Interferon-gamma release assay IPT Isoniazid preventive treatment IRIS Immune reconstitution inflammatory syndrome LF-LAM Lateral flow urine lipoarabinomannan assay LFT Liver function test LTBI Latent tuberculosis infection MDR-TB Multidrug-resistant TB MMD Multi-month dispensing PEPFAR President’s Emergency Plan for AIDS Relief PLHIV People living with HIV PMTCT Prevention of mother-to-child transmission PHC Primary healthcare RPC Repeated prescription collection SDGs Sustainable development goals TB Tuberculosis TBTC Tuberculosis Trials Consortium TIER Three interlinked electronic registers TLD Tenofovir / Lamivudine / Dolutegravir TPT TB preventive treatment TST Tuberculin skin test UN United Nations WHO World Health Organization Xpert GeneXpert MTB/RIF (Ultra, or latest recommended version) 3HP 3 months of weekly isoniazid plus rifapentine 3RH 3 months of daily rifampicin plus isoniazid 6H 6 months of daily isoniazid monotherapy 12H 12 months of daily isoniazid monotherapy 3  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION LIST OF DEFINITIONS Adherence The extent to which a person’s behaviour corresponds with agreed recommendations from a healthcare worker for taking medication, following a diet and/or making lifestyle changes Adolescent A person aged 15 to 19 years Child For practical purposes, children weighing >25kg (typically eight to ten years of age) can be treated with adult doses of TB medications including for TB preventive treatment (TPT). Children weighing >25kg can also usually produce sputum for TB testing. For reporting purposes, children are defined as 0 to 14 years of age by WHO. Evaluation The periodic assessment of the change in targeted results that can be attributed to the programme intervention, or the analysis of inputs and activities to determine their contribution to results Infant A child under one year of age Index patient A person (adult or adolescent) with infectious pulmonary TB Latent TB A state of immune response to stimulation by Mycobacterium tuberculosis antigens, infection indicated by a positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA) test, with no evidence of active TB disease Monitoring The tracking of key elements of programme performance (inputs, activities and results) on a regular basis to provide continuous information on progress towards achieving goals, and alert staff and managers to problems, providing an opportunity for these to be resolved early Recent TB Contact with a person diagnosed with pulmonary TB in the last 12 months. The person exposure may be from the same household, or be a close contact outside of the household setting, e.g., a care provider, colleague, teacher, family member or friend Significant TB Known exposure to a person (adult or adolescent) with pulmonary TB who shared exposure the same enclosed space for one or more nights or for frequent or extended daytime periods during the three months before the index patient starting their TB treatment. Significant TB exposure can occur in any setting, e.g., the household, workplace, place of learning or care. Therefore, the term “household contact” is confusing since it is limited in scope and should no longer be used. “TB contact” will therefore be used throughout this document. TB contact All people (family members and other individuals; regardless of age and HIV status) who have had a ‘significant TB exposure’ – that is: shared the same enclosed space or shared living arrangement with a TB index patient for one or more nights or for frequent or extended daytime periods during three months before the start of current treatment in the TB index patient with pulmonary TB TB disease Disease caused by Mycobacterium tuberculosis. TB can either be bacteriologically confirmed or clinically diagnosed TB exposed Infants born to mothers who were diagnosed with TB before or after the baby was infants born, or other documented close TB exposure in the infant (e.g. another caregiver, family member, day care provider) Silicosis Lung fibrosis caused by the inhaling silica-containing 3HP three months of weekly isoniazid plus rifapentine 3RH three months of daily rifampicin plus isoniazid 6H six months of daily isoniazid monotherapy 12H 12 months of daily isoniazid monotherapy 4  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION EXECUTIVE SUMMARY Rationale for expanded eligibility for without symptoms, neither sputum testing nor chest TPT: A TB test and treat approach x-ray (CXR) are therefore requirements to start TPT. Sputum testing should be attempted in children who It is essential that TB preventive treatment (TPT) is can expectorate spontaneously (typically >=25kg), scaled up to reduce the burden of TB in South Africa. but if they are well (without symptoms) and unable to Previously, TPT was offered only to people who were expectorate, they should start TPT, even if no CXR or at the highest risk of progressing to TB disease after sputum testing is available. exposure (i.e., children younger than five years of age, and all people living with HIV, regardless of age). If unable to produce sputum, people considered for However, to achieve TB elimination, it is imperative TPT should undergo clinical evaluation as a minimum, to implement TPT more comprehensively for and a CXR where available. Other samples should be everyone with significant TB exposure and all considered as clinically relevant. CXR is a valuable other individuals at high risk of TB. Diagnostic tool to rule out TB disease in adults and in children, evaluation processes, TPT initiation processes, TPT but its absence should not pose a barrier to starting regimens, and clinical evaluation at follow-up will vary TPT in anyone – especially in children, if they are well by age, HIV status, and pregnancy status. However, and have no symptoms. TB testing and TPT should be offered to all people with significant TB exposure or who have a high risk If test availability varies by setting, TB testing of TB disease progression – i.e. a TB test and treat deficiencies should be urgently addressed in parallel (offering either TPT or active TB treatment) approach. to excluding active TB disease and encouraging The use of shorter duration TPT regimens, where TPT access. The National TB Prevalence Survey1 possible, will reduce the burden of TPT treatment on has highlighted the high burden of asymptomatic individuals, households and on health services. TB amongst adults and adolescents, reflecting the importance of having a low threshold for testing In most instances, people who should be offered people for active TB, especially before offering TPT, TPT will share a household with at least one person including in people not historically considered to be at who is concurrently on TB treatment. Therefore, high risk of TB disease. where possible, a ‘family-centred’ approach to TPT initiation and adherence support should be It is important to recognise the difference between adopted by integrated healthcare worker teams or testing for TB infection (e.g., TST, IGRA) and testing health services where possible. It is also important for TB disease (Xpert/culture, chest x-ray, LF- to consider the context of the household, and to offer LAM). Tests for TB infection are useful to detect TB similar regimens to affected household members, infection, and to predict who is at the highest risk of where possible. developing TB disease, but are not a requirement to starting TPT. If tests of infection are not available, TB test and treat approach: It is essential to rule this should not pose a barrier to TPT initiation. A out TB disease before initiating TPT. Therefore, all positive test of TB infection means that the person is individuals (adults, adolescents, children and infants) (or was previously) infected with M.tb, but does not should always be evaluated for TB disease before indicate (or exclude) TB disease. Also, a negative initiating TPT, including testing for active TB disease. test of TB infection does not mean that the person Thereafter, the next decision, in the presence of is not actually infected with M.tb or is not at risk for significant TB exposure or TB risk, is to either offer developing TB disease in the near future. Therefore, TB treatment (in the presence of disease) or to tests of TB infection are no longer listed in these offer TPT. In the past, uncertainty over diagnostic algorithms and not are not requirement to initiate requirements and the limited availability of diagnostic TPT. Any lack of availability of tests of TB infection tools were significant barriers to TPT access. The should not impact whether somebody is offered TPT guiding principle for these revised guidelines is to or not. In individual clinical scenarios, tests of TB help overcome several of these barriers. infection may be used by clinicians as available as useful tests to determine TB infection status and the All people considered for TPT should undergo risk future disease progression. clinical evaluation (symptom check and physical examination) and be tested with GeneXpert (Xpert), In contrast, testing (clinical evaluation and other test) even if asymptomatic. TB testing strategies will vary for TB disease is required before disease can be by age as younger children cannot spontaneously ruled out and should be made available to all people expectorate sputum. Other clinically relevant before being offered TPT (refer to the section on samples should be considered in children (gastric children for exceptions as clinically relevant). aspirates, fine needle aspirates, stool). In children 5  National Guidelines on THE TREATMENT OF TUBERCULOSIS INFECTION People who require TPT People who have previously had TB (TB survivors) are at higher risk of getting TB again and should be TB contacts: All adults, adolescents and children considered for treatment of infection after another (including newborns or infants) exposed to TB require significant TB exposure. TPT once TB disease has been excluded through evaluation – irrespective of HIV status, pregnancy, or Silicosis: People with silicosis have a significant risk previous TB disease or treatment status. Significant of developing TB disease and should be considered TB exposure can occur in any setting, e.g. in the for treatment of infection regardless of significant TB household, workplace, place of learning or care, or exposure. other. Therefore, the term “household contact” is confusing (the definition is too narrow) and should Choice of regimen no longer be used. Going forward, the term “TB contacts” should therefore be used. After each TB In South Africa, the current TPT options include exposure, the exposed person must be evaluated isoniazid and rifapentine given once weekly for three for TB again and either TB treatment or TPT should months (3HP), daily rifampicin and isoniazid for offered (e.g., repeat TB test and treat approach after three months (3RH), daily isoniazid for six months each significant TB exposure). TPT is only effective (6H) or daily isoniazid for 12 months (12H). As a while it is being given, so previous TPT does not rule, shorter treatment options should be offered protect against a new TB exposure. where feasible and available. If 3HP is not available (or contra-indicated), 3RH or 6H should be offered All pregnant women with significant TB exposure for people who tested negative for HIV, and 12H for (irrespective of age or HIV status) should be offered PLHIV (6H for children with HIV) and 3RH for children TPT once TB disease has been excluded through