LIST OF CONTRIBUTORS....................................................................xiii GLOSSARY............................................................................................xv ABBREVIATIONS..................................................................................xvi
CHAPTER 1: BACKGROUND INFORMATION ON
TUBERCULOSIS PREVENTIVE TREATMENT .....1 1.1 Background and Rationale.............................................................1 1.2 Target Audience.............................................................................2 1.3 Purpose.........................................................................................2 1.4 Development of the guidelines......................................................2 1.5 Situational analysis for provision of TPT in the country.................3 1.6 Programmatic management of TB preventive treatment...............3
CHAPTER 2: POPULATION GROUPS ELIGIBLE FOR
TUBERCULOSIS PREVENTIVE TREATMENT .....5 2.1 Identification of risk populations for TPT treatment........................5 2.1.1 People living with HIV.........................................................5 2.1.2 HIV-negative household contacts of bacteriologically con firmed pulmonary TB patients..............................................6 2.1.3 Other at-risk population groups...........................................6
CHAPTER 3: RULING OUT TB DISEASE BEFORE TB
PREVENTIVE TREATMENT....................................7 3.1 Targeted populations at high risk of contracting TB disease..........7 3.1.1 People living with HIV.........................................................7 3.1.2 HIV-negative clients with history of TB contact.....................7 3.1.3 Other at-risk population groups...........................................7 3.2 Algorithms for ruling out active TB disease among risk population...8 3.2.1 Algorithm for People living with HIV.....................................8 3.2.2 Algorithm for HIV negative clients.....................................10 3.3 Tests for TB infection.....................................................................11 3.3.1 Interferon-Gamma Release Assay (IGRAs).....................11 3.3.2 The Mantoux tuberculin skin test (TST)............................11 3.3.3 Mycobacterium tuberculosis antigen-based skin tests (TBSTs).............................................................................12
iii CHAPTER 4: TUBERCULOSIS PREVENTIVE TREATMENT..............13 4.1 Definition and rationale for TPT...................................................13 4.2 Benefits of provision of TPT.........................................................13 4.2.1 Population level benefits...................................................13 4.2.2 Individual benefits.............................................................13 4.3 Eligibility criteria for provision of TPT............................................14 4.4 Recommended TPT regimens....................................................15 4.4.1 Three months of weekly isoniazid plus rifapentine (3HP)...15 4.4.2 Three months of daily isoniazid plus rifampicin (3HR)........15 4.4.3 Six months of daily isoniazid monotherapy (6H) ..............15 4.4.4 Pyridoxine........................................................................19 4.5 Management of close contacts of a drug-resistant tuberculosis pa tient.............................................................................................19 4.6 Future development in TPT.........................................................20 4.7 Drug-Drug Interactions with Antiretroviral..................................20 4.7.1 Rifamycins and ARVs.......................................................20 4.7.2 Rifamycins and other Medication......................................20 4.8 Adverse Reactions, Monitoring and Management......................24 4.8.1 Adverse reactions to TPT drugs.......................................24 4.8.2 Management of adverse events.......................................26 4.9 Pharmacovigilance and Surveillance of TPT Drug Adverse Reactions....................................................................................28 4.9.1 Aim of Pharmacovigilance................................................28 4.9.2 Reporting ADRs................................................................28 4.9.3 Modalities of reporting in passive method........................28 4.9.4 What to report....................................................................29 4.9.5 Who should report.............................................................29 4.9.6 When to report...................................................................29 4.9.7 Where to submit report.....................................................29
CHAPTER FIVE: ADHERENCE AND ETHICAL CONSIDERATIONS..31
5.1 Adherence...................................................................................31 5.2 Factors that influence adherence of TPT among all eligible clients..........................................................................................31 5.3 Factors that enhance adherence of TPT among all eligible clients..........................................................................................31 5.3.1 Client related factors.........................................................31 5.3.2 Health system factors.......................................................31 5.3.3 Regimen related factors....................................................32 5.4 Effective patient-centred approach to promote adherence..........32 5.5 Treatment completion..................................................................33
iv 5.6 Treatment interruption.................................................................33 5.7 Special considerations................................................................34 5.8 Ethics in TBI services....................................................................35 5.9 Key implementation aspects in ethical consideration...................36 5.9.1 Raising awareness...........................................................36 5.9.2 Prerequisites on health care delivery in the context of ethics................................................................................36 5.9.3 Feedback from clients.......................................................37 5.9.4 Assessment tool to measure adherence in each visit, the data captured should be analysed to inform programmatic actions and decisions.......................................................37
CHAPTER 6: COMMUNITY ENGAGEMENT.......................................39
6.1 Community TB services...............................................................39 6.2 Community Right and Gender (CRG) in TPT...............................39 6.3 Community Led Monitoring (CLM)..............................................39 6.3.1 Programmatic Management of TPT (PMTPT) in Community settings........................................................................................40 6.3.2 Role and responsibilities of Community Health Workers...41 6.3.3 Role and responsibilities of Facility Health Care Workers..42 6.3.4 Role and responsibilities of the CSOs..............................42 6.4 Integrating TPT and other routine services.................................43 6.5 ACSM Support for TB Infection Management.............................43 6.5.1 Principles of ACSM..........................................................43 6.5.2 The roles of ACSM strategy on TB Infection.........................44 6.5.3 Priority ACSM activities in TPT..........................................44
CHAPTER 7: PROCUREMENT AND SUPPLY CHAIN MANAGEMENT..45
7.1 Procurement, Storage and Distribution.......................................45 7.2 Reconciliation..............................................................................46 7.3 Roles and responsibilities of TB commodity (3HP, 3HR & 6H) man agers...........................................................................................47 7.3.1 Health care provider..........................................................47 7.3.2 DOT provider.....................................................................47 7.3.3 DTLC/DACC/DTHO .........................................................47 7.3.4 Facility Pharmacist............................................................48 7.3.5 District Pharmacist............................................................48 7.3.6 RTLC/RACC/Regional Pharmacist...................................48 7.3.7 MSD..................................................................................49 7.4 Quantification and quantification assumptions............................49 7.4.1 Quantification....................................................................49
v CHAPTER 8: MONITORING, EVALUATION AND LEARNING.............51 8.1 Data collection, reporting and data storage..................................51 8.2 List of data collection tools..........................................................51 8.3 Analysis and use of data..............................................................52 8.3.1 Use of data........................................................................52 8.3.2 Data Quality Assurance.....................................................53 8.3.3 Data flow...........................................................................55 8.4 Focused supportive supervision...................................................56 8.5 Documentation of best practice and research questions.............57 8.6 Mobile Health Platforms..............................................................57
Table 1: Characteristics of available TPT regimens (Source WHO
Operational Handbook on tuberculosis: Module 1: Prevention).......................................................................16 Table 2: Recommended Regimens for the treatment of tuberculosis infection............................................................................18 Table 3: Recommended dosage for the treatment of tuberculosis in fection ...............................................................................18 Table 4: Drug-drug interactions between Rifamycin based TPT and ARVs................................................................................21 Table 5A: Drug-drug interactions between Rifamycin based TPT and available ART regimens in Tanzania.................................22 Table 5B: Drug-drug Finteractions between Rifamycin based TPT and other medications.............................................................23 Table 6: Management of potential adverse reactions following treat ment with TPT...................................................................27 Table 7: Data quality terms.............................................................54 Table 8: NTLP/NACP data quality activities…………........………..55 Table 9: Best practice documentation……....……………………….57
vii LIST OF FIGURES
Figure 1: Algorithm for ruling out TB; for children above 12 months, Adult and adolescent including pregnant women and breast feeding mothers living with HIV.........................................9 Figure 2: Algorithm for ruling out active Tuberculosis among other risk groups........................................................................10 Figure 3: Flow of information, TPT commodities and R & R form ...46 Figure 4: Data Flow.........................................................................56
viii FOREWORD
Worldwide, TB is the 13th leading cause of death and the second leading infectious killer disease after COVID-19 (above HIV/AIDS). Globally millions of people continue to fall sick from TB each year; in 2021, an estimated 10.6 million people fell ill from TB (which was an increase of 0.5 million from 10.1million in 2020), and of these, 1.6 million people died from TB.
Tuberculosis infection is a state of persistent immune response to
stimulation by Mycobacterium tuberculosis antigens with no evidence of signs and symptoms of TB disease. People with TB infection are at risk of developing active TB infection, serving as the breeding ground for the TB epidemic in the community. TB preventive treatment is offered to individuals at risk of developing TB disease to reduce that risk.
The fifth National TB and Leprosy Strategic Plan (NSP VI 2020-2025)
targets to offer TB preventive treatment to at least 90% of eligible individuals at risk. These populations are as follows: People living with HIV, under five and above five household contacts of bacteriologically confirmed PTB patients, prisoners, miners, PWUD, and elders.
These guidelines for managing TB infection aim to provide a framework
to guide the management of TB infections as a critical strategy to end TB by 2030 in Tanzania. This will be achieved through the programmatic management of TPT by systematically implementing evidence-based interventions on identifying the at-risk populations, screening them, offering a timely diagnosis and effective treatment options, and monitoring treatment completion.
These guidelines for managing TB infections also offer guidance to all
stakeholders on managing TB infections in Tanzania. The development of these guidelines has been a participatory process by all stakeholders. I believe that we will all put efforts into ensuring the implementation and monitoring of the objectives in these guidelines. Let us work together to End TB in Tanzania.
Prof. Tumaini J. Nagu
CHIEF MEDICAL OFFICER
ix ACKNOWLEDGMENT
The development of this first edition of 2022 guidelines on the management
of TB infection has involved multiple consultative meetings and reviews that engaged local and international experts on TB, DR-TB, and TB/ HIV (see the list of contributors). I want to acknowledge experts working at MoH, PORALG, USAID, WHO, KNCV, KIDH, CDC, UMB, EGPAF, NIMR, THPS, CUHAS and BMH for their outstanding contributions and coordination efforts for the development of these guidelines.
The development of these guidelines was guided by the National TPT
Expert Committee (NTEC) and World Health Organization (WHO) recommendations on treating TB infection. I take note of the support from the office of the Permanent Secretary, Chief Medical Officer, and Directorate of Preventive and Curative services. I also note the contributions of the former Chief Medical Officer (Dr. Aifello Sichalwe) during the preparation of these guidelines. I will be short of gratitude if I do not recognize the efforts of Dr. Beatrice Mutayoba (DPS) who by then NTLP was under her directorate. I also recognize the stewardship and guidance of the NTLP led by Dr. Riziki Kisonga, Program Manager. Furthermore, I convey my gratitude to Dr. Peter Neema, NTLP TB/HIV coordinator for his marvelous efforts during the whole process of preparation of these guidelines. I wish to convey my sincere gratitude to NTEC members and the expanded team that worked tirelessly to ensure the successful completion of these guidelines.
Dr. Catherine Joachim
HEAD OF PROGRAMS
x EXECUTIVE SUMMARY
The overall structure of these guidelines and recommendations follows
the logical cascade of management of TB infection (TBI). Identification of at-risk populations, including adults and children living with HIV, all household contacts of bacteriologically confirmed PTB patients, prisoners, miners, people who use drugs (PWUDs), and elders; ruling out active TB disease, testing for TBI, providing treatment, monitoring adverse event, adherence to and completion of treatment and Monitoring and evaluation. Overall, without treatment, about 5 to 10% of infected persons will develop TB disease at some time in their lives. About half of those people who develop TB will do so within the first two years of infection. For persons whose immune systems are weak, especially those with HIV infection, the risk of developing TB disease is considerably higher than for persons with normal immune systems. Therefore, it is essential to identify those at the highest risk of progression to active TB and manage TBI, as not all individuals infected with M. tuberculosis develop active TB. Currently, there are no predictive tests to identify individuals who will progress to TB disease; a targeted approach would be an appropriate public health response.
Adherence to the TB preventive treatment (TPT) regimens throughout
the course and treatment is an essential determinant of clinical benefits. Poor adherence and early cessation of TPT can potentially increase the risk of individuals developing active TB disease, including drug resistance TB. Since the success of the TPT strategy is based on adherence to treatment, meticulous monitoring and appropriate management of any adverse events is essential.
Prevention of TB through TPT begins with diagnosing TBI and excluding
active TB among high-risk individuals. Prevention of TB disease by treatment of TBI is a critical component of the National Strategic Plan (NSP VI) 2020-2025 for ending TB in Tanzania. The NSP VI proposes a Detect-Treat-Prevent-Build approach and introduces and scales up new TPT regimens.
These guidelines are organized in chapters with sub-sections, figures,
and annexed materials to guide users step by step as they manage the TB infection cascade. The first chapter provides an overview of the Programmatic arrangement and the Management of Tuberculosis Infection. It also envisages a scope and rationale, policy direction, and
xi framework, describing the audience and the expected benefits to the targeted population. Chapter two describes the targeted population on how to reach and link them to testing and care. Chapter three describes algorithms for clinical assessment of PLHIV, children aged under five, and other targeted risk groups for diagnosing TB infection and ruling out active TB diseases. It entails introducing new testing technology, follow-up, and linking to care, and emphasizing health care workers (HCWs) on ensuring quality TBI services, including diagnosis, handling, and logistic support.
Chapter four narrates on TB preventive treatment modalities; it describes
the options for TBI treatment, including convention six-month Isoniazid (INH) and new short TPT regimens of three-month Isoniazid and Rifampicin (3HR) for children and three-month Isoniazid and Rifapentine (3HP) for adults and the scale-up plan as NTEC has recommended it. Chapter five reports on adherence and ethical consideration and clarify the vital implementation aspects of ethics in TB infection services. Chapter six recounts the management of contacts from different groups and situations, community and advocacy, communication and social mobilization (ACSM); it expands different approved approaches to conducting contact investigation and implementing TPT at Community and ACSM.
Chapter seven highlights procurement and supply management of TPT
medicines and elaborates on assumptions of TPT provision in Tanzania as recommended by NTEC. Monitoring, Evaluation, and Learning are included in Chapter eight, which shed light on results-based management tools to assess progress made toward tracking implementation and achieving TBI goals, information management using DHIS2-ETL, essential commodities consumption, analysis and use of TB infection data, supportive supervision and operational research.
These guidelines will now be implemented across Tanzania to gain and
document experiences on feasibility, safety monitoring, and enhancement in desirable treatment outcomes of TB infection to further guide the country in its refinements as National and global evidence emerges in the future and expansion of coverage of people at risk.
xii LIST OF CONTRIBUTORS S/N Name Organization 1 Dr. Beatrice Mutayoba MOH-DPS 2 Dr. Riziki Kisonga MOH-NTLP 3 Dr. Annath Rwebembera MOH-NACP 4 Dr. Mageda Kihulya Pastory PO-RALG 5 Dr. Liberate Mleoh MOH-NTLP 6 Dr. Allan Tarimo MOH-NTLP 7 Dr. Boniface MOH-NACP 8 Dr. Emmanuel Matechi MOH-NTLP 9 Dr. Deus Kamara MOH-NTLP 10 Dr. Boniface Silvanus MOH-NACP 11 Dr. Peter Neema MOH-NTLP 12 Dr. Isaya Jelly MOH-NACP 13 Prof. Samwel Kaluvya CUHAS 14 Prof. Sayoki Mfinanga NIMR-Muhimbili 15 Prof. Stella Mpagama KIDH 16 Dr. Peter Mbelele KIDH 17 Dr. Zuweina Kondo TB-Consultant 18 Dr. Issa Sabu NIMR-Mbeya 19 Dr. Judith Phillip MOH-NTLP 20 Dr. Siraji Shabani MOH-NACP 21 Mr. Emmanuel Nkiligi MOH-NTLP 22 Dr. John Msaki MOH-NTLP 23 Mr. Jumanne M. Mkumbo MOH-NTLP 24 Mr. Julius Mtemahanji MOH-NTLP 25 Mr. Galus A. Sililo MOH-NTLP 26 Dr. Bhavin Jani USAID 27 Dr. Ezra Mwijarabu USAID 28 Dr. Daniel Magesa CDC 29 Dr. Lillian Mtei KNCV 30 Dr. Anna Kiravu MDH 31 Dr. Wanze Kohi UMB 32 Dr. Nelson Jonas THPS 33 Dr. Hassan Mattaka MDH 34 Dr. Chacha D. Mangu NIMR-Mbeya 35 Mr. Ramadhani Kingalu MOH-NTLP (CTRL) 36 Miss. Daphne Mtunga MOH-NTLP (CTRL) 37 Bahati Wiliard Myombe NIMR-Dodoma 38 Dr. Mandala Adam RS-Manyara 39 Dr. Hawa Ngasongwa Morogoro Regional Referral Hospital 40 Dr. Dickens Bwana MKUTA 41 Dr. Isack Kiduma Benjamin Mkapa Hospital 42 Mr. Chrispin Mamkinga MOH-NTLP 43 Miss. Adelina Wissa MOH-NTLP 44 Mr. Jonathan Nyamwela MOH-NTLP 45 Mr. Patrice Makao MOH-HPS
xiii 46 Mr. Romantiezer Robert Mbassa MOH-NTLP 47 Mr. Emmanuel B. Kimario MOH-NACP 48 Dr. Fred I. Lwilla TB/HIV Expert 49 Mr. Said Mayanja MOH-CP 50 Dr. Ackim Mwaikasu TB/HIV Expert 51 Mr. Cornel Matiku Wambura TB/HIV Expert 52 Mr. Oney Godson Lwanzali MOH-NTLP 53 Mr. Juma Said MOH-NTLP 54 Mr. Prosper Kilasara Msaki MOH-NTLP 55 Miss. Prisca Jackson MOH-NTLP 56 Mr. Collins Minja MOH-NTLP 57 Dr. Jacob Mwanamtwa Babati DC 58 Dr. Raphael Mumba RS-Tanga 59 Dr. Mbarouk Seif Dar es Salaam CC 60 Dr. Aden Mpangile RS-Pwani 61 Dr. William Mtumbuka TB/HIV Expert 62 Dr. Mohamed A Mohamed ORCI 63 Valeria R Haroub ZIHHTLP 64 Dr. Robert Kisanga ICAP 65 Dr. Godwin Munuo Amref 66 Dr. Edward Mwesiga EGPAF 67 Dr. Khamis Kulemba RS-Simiyu 68 Dr. Philipo Lambo Sheneneko MOH-NACP
xiv GLOSSARY
Community Led Monitoring: Is a community-based mechanism by
which service users and/or local communities gather, analyse and use information on an ongoing basis to improve access to, quality and impact of services, and to hold service providers and decision makers to account.
Contacts of TB/DR-TB patients – Person living in the same household
or spend prolonged hours a day with a patient in the same indoor settings with the TB/DR-TB.
HIV+ index contacts – These are sexual partners or biological children
of less than 15 years of HIV+ clients.
Pharmacovigilance – Pharmacovigilance is the science and activities
relating to the detection, assessment, understanding, and prevention of adverse events or any other medicine/vaccine related problem.
Shorter TPT regimens Transition – This is the transition from 6H to 3HP
and 3HR as TPT medicines.
Shorter TPT medicines – This means provision of:
a. Three months of weekly rifapentine plus isoniazid b. Three months of daily rifampicin plus isoniazid
Tuberculosis Infection (TBI) – A state of persistent immune response
to stimulation by M. tuberculosis antigens with no evidence of clinically manifest active TB. This is also at times referred to as TB infection. There is no gold standard test for direct identification of M. tuberculosis infection in humans. Most infected people have no signs or symptoms of TB but are at risk for active TB disease.
Tuberculosis Preventive Treatment (TPT) – Treatment offered to
individuals who are considered at risk of TB disease to reduce that risk.
xv ABBREVIATIONS
3HP - Three months of weekly Rifapentine and Isoniazid
3HR - Three months of daily Rifampicin and Isoniazid 3TC - Lamivudine 6H - Six months of daily isoniazid monotherapy ABC - Abacavir ACF - Active TB case finding aDSM - Active Drug Safety Monitoring ACSM - Advocacy, communication and social mobilization ADR - Adverse Drug Reaction AIDS - Acquired immunodeficiency syndrome ART - Antiretroviral therapy ARV - Antiretroviral drugs BCG - Bacilli Calmette – Guerin (vaccine) CBHS - Community based HIV services CHW - Community health worker CLHIV - Children living with HIV CLM - Community Led Monitoring CRG - Community, Rights and Gender DDI - Drug-drug Interactions DDR - Drug-drug reactions DSD - Differentiated service HIV delivery ELISA - Enzyme-linked immunosorbent assay EMR - Electronic medical records FDC - Fixed dose combination HHC - Household contacts of bacteriologically confirmed TB patient HIV - Human immunodeficiency virus HMIS - Hospital management information system ICF - Intensified TB case finding IEC - Information, education and communication materials IFN-g - Interferon gamma assay IGRA - Interferon-gamma release assay ILS - Integrated logistic system INSTIs - Intergrase strand transfer inhibitors IPT - Isoniazid preventive therapy IPs - Implementing partners LF-LAM - Lateral flow urine lipoarabinomannan assay LFT - Liver function test LGA - Local Government Authority
xvi LMIS - Logistic management information system LTBI - Latent tuberculosis infection MDR - Multidrug resistant tuberculosis M&E - Monitoring and evaluation MTB - Mycobacterium tuberculosis NNRTIs - Non-nucleoside reverse transcriptase inhibitors NRTI - Nucleoside reverse transcriptase inhibitor PI - Protease inhibitors PMTCT - Prevention of mother-to-child transmission PMTPT - Programmatic management of TB preventive treatment PWUDs - People Who Use Drugs SOP - Standard operating procedure TB - Tuberculosis TBI - Tuberculosis Infection TDF - Tenofovir disoproxil fumarate TBST - Mycobacterium Tuberculosis antigen-based skin tests TPT - Tuberculosis preventive treatment TST - Tuberculosis skin test U5HHC - Under five household contacts WHO - World Health Organization
xvii xviii CHAPTER 1: BACKGROUND INFORMATION ON TUBERCULOSIS PREVENTIVE TREATMENT
1.1 Background and Rationale
Tanzania is among the 30 high TB burden countries, with an annual estimated TB incidence of 208/100,000 and death rate of 29/100,000 in 20211. The country’s national TB program notified 86,701 new TB cases in 2021. Of the total TB cases notified, 43% were bacteriologically confirmed pulmonary TB patients2.
TB infection (TBI) is defined as a state of persistent immune response
to stimulation by Mycobacterium tuberculosis (MTB) antigens with no evidence of clinically manifested active TB. Persons with TB infection are not infectious and cannot spread TB infection to others. According to WHO, it is estimated that about one-fourth of the world’s population is infected with MTB.
On average, 5-10% of those with TBI will develop active TB disease
during their lives usually within the first two years after initial infection. The risk for active TB disease after infection depends on several factors, the most critical being immunological statuses such as HIV infection, severe malnutrition, diabetes, patients on immunosuppressive therapy and infants and children under-fives. The provision of TB preventive treatment (TPT) has proven itself an effective intervention to avert the development of active TB disease, with efficacy ranging from 60% to 90%3.
Tanzania started implementation of TPT back in 2005 whereby it was
given to children under-five household contacts of bacteriologically confirmed TB patients and provided at TB clinics. Upon 2011, the TPT was extended to include all people living with HIV (PLHIV) and Isoniazid Preventive Therapy (IPT) was solely given as the TPT. Tanzania has about 1,544,663 PLHIVs out of the estimated 1,700,000, of which 1,312,963 (85% of PLHIV current on care) have already been provided with 6H by December 20224. Even though, the UN high-level meeting of TB (UNHLM) target of providing TPT to 574,000 PLHIV has been surpassed, yet the national target of providing TPT to 97% of PLHIV on care has not been reached. Furthermore, the UNHLM U5HHC target of providing TPT to 119,900 children within four years (2018-2022) has not been reached, only 62% (12,925 children out of 20,718 targeted children in 2020) of the national target received TPT in 2020 5. 1 WHO Global TB report 2022 2 NTLP programmatic data 2021 3 World Health Organization. (2018). Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. World Health Organization. https://apps.who.int/iris/handle/10665/260233. License: CC BY-NC-SA 3.0 IGO 4 NACP data. 5 UNHLM targets for Tanzania (2018-2022)
1 The UNHLM targets of providing TPT to other household contacts (≥5years) of bacteriologically confirmed TB patients have not been reached since TPT was not agreed to be provided in those group.
Programmatic management of TBI consists of systematic interventions to
identify and treat those with the TB infection. Three key considerations are addressed in these guidelines: determining priority eligible populations based on the national context, diagnosing individuals with TBI from priority populations, and providing cost-effective treatment preferably shorter TPT regimens.
The recommendations in these guidelines align with pillar one of the WHO End TB strategies of providing integrated patient-centred prevention through expanding treatment of persons at high risk of Tuberculosis and the NSP VI objective of strengthening the management of co-morbidities, including collaborative TB/HIV services.
1.2 Target Audience
The target audiences for these guidelines are:
• The Ministry of Health, PO-RALG and other government institutions. • Stakeholders working in TB and HIV areas, including research and academic institutions. • Healthcare providers in public and private facilities and community healthcare workers. • Development partners, Implementing partners and Civil Society Organisations.
1.3 Purpose The main purpose of these guidelines is to provide updated technical guidance and recommendations in implementing the programmatic management of TBI in the country by all stakeholders. This document will also be used as a reference to guide the screening, diagnosis, treatment, monitoring and evaluation of TB infections in the country.
1.4 Development of the guidelines
The Ministry of Health through NTLP and NACP, led the process of developing these guidelines. There was also, decisive engagement of TB stakeholders from LGAs, CSOs, academic and research institutions representatives in providing field experience and evidence-based interventions. Development and Implementing partners were also involved in the process, particularly in the systematic reviews to provide their insights and experience from the field.
2 1.5 Situational analysis for provision of TPT in the country This section provides information on the current situation on programmatic implementation of TPT in the country based on strengths, weaknesses, opportunities available and critical threats (SWOT analysis) as follows: Strength:
i. TB preventive treatment is provided to all eligible PLHIV and under five
household contacts of bacteriologically confirmed TB patients. ii. There are policy guidelines for Collaborative TB/HIV activities which stipulates the provision of TB infection prevention among risk populations. iii. Presence of a robust supply chain management system for TB medicines. iv. Availability of health system infrastructure and human resources. v. Presence of NTEC. vi. Presence of well-coordinated TB and HIV programs. vii. Strong collaboration between MOH, PO-RALG and other government institutions. Weakness: i. TPT coverage has not met the National target of 97%. ii. TPT completion rate for PLHIV is below target of >85Inadequate capacity among HCWs in the management of TPT (screening, diagnosis and treatment monitoring). Opportunities:
i. Readiness and commitment of IPs and Stakeholders to support TPT scale
up. ii. Global and national political will to End-TB 2035. iii. Existence of TB community systems including CHWs and Ex-TB groups who can support CI and adherence. iv. Presence of HIV service delivery models. Threats:
i. Slow adoption of new TPT shorter regimen.
ii. Scarcity of resources.
1.6 Programmatic management of TB preventive treatment
This approach has been a low-priority intervention for the National program due to other competing priorities. Advocacy efforts at different levels are critically important to ensure that all individuals at risk of developing TB are identified and treated.
3 At each step of the cascade of care, all TPT stakeholders should: • Earmark investment to strengthen health systems and enhance human resource. • Build capacity of health care workers to ensure they have adequate knowledge and skills of TPT. • Create demands from the users (clients) so they can be empowered to ask for the provision of TPT. • Strengthen supervision and monitoring in collaboration with the facility health management teams (HMTs), council health management teams (CHMTs) and the regional health management teams (RHMTs). • Ensure all health care workers abide by the current National policy guidelines.
4 CHAPTER 2: POPULATION GROUPS ELIGIBLE FOR TUBERCULOSIS PREVENTIVE TREATMENT
2.1 Identification of risk populations for TPT treatment
Not all individuals infected with M. tuberculosis develop active TB. The risk is particularly high among children younger than five years, people with compromised immunity, and individuals exposed to silica. As preventive treatment entails risks and costs, preventive treatment of M. tuberculosis infection should be selectively targeted to the population groups at highest risk for progression to active TB disease, who would benefit most from the treatment of TBI4.
The following are at-risk populations eligible for systematic TBI screening, testing, and treatment modalities.
2.1.1 People living with HIV
HIV infection weakens a person’s immunity to TB. Therefore, the main focus of action and efforts need to be intense in recognizing the increasing proportion of TB patients in this group and preventive TB treatment should be offered to this group. i. Adults, adolescents, and children living with HIV should be screened for TB disease. Those who screen negative should be offered TB preventive treatment. Adults and adolescents living with HIV, with unknown or a positive tuberculin skin test (TST) are unlikely to have active TB and should receive TB preventive treatment as part of a comprehensive package of HIV care. TBI testing by TST or IGRA is not a requirement for initiating TB preventive treatment in people living with HIV. TB preventive treatment should also be provided to pregnant women on PMTCT services or those on antiretroviral treatment who have previously been treated for TB disease. ii. Children aged ≥ 12 months living with HIV who are considered unlikely to have TB disease based on clinical screening for symptoms should be offered TPT as part of a comprehensive package of HIV prevention and care. iii. Infants aged < 12 months living with HIV who are in contact with a TB patient and investigated for TB should receive TPT if the investigation shows no TB disease.
WHO operational handbook on tuberculosis. Module 1: prevention - tuberculosis preventive treatment.
6
Geneva: World Health Organization; 2020. License: CC BY-NC-SA 3.0 IGO.
5 2.1.2 HIV-negative household contacts of bacteriologically confirmed pulmonary TB patients i. Children under five years who are household contacts of people with bacteriologically confirmed pulmonary TB and who are found not to have active TB on an appropriate clinical evaluation should receive TPT. TBI testing is not a requirement for initiating TPT in this age group. ii. Children aged 5 years, adolescents, and adults who are household contacts of people with bacteriologically proven pulmonary TB and are found not to have active TB by an appropriate clinical evaluation and following TBI testing confirmation. iii. TB preventive treatment for household contacts of patients with multidrug-resistant tuberculosis shall be recommended based on an individualized risk assessment, DST results, and clear clinical reason. There is now no TPT indicated for contacts of patients with DR-TB, however operational research is ongoing.
2.1.3 Other at-risk population groups
i. Other at-risk groups to receive TPT in Tanzania include prisoners, PWUDs and miners. They should be given TPT after exclusion of active TB disease based on the clinical algorithm and after testing confirmation of TBI. The provision of TPT in this group will wait for the decision of whether TBI testing is needed and availability of TBI testing in the country. ii. TPT for other at-risk groups including people who are on immune- suppressant drugs, or receiving hemodialysis, on transplant, diabetes mellitus patients, malnourished children, refugees, and health care workers in the facility settings lack enough evidence and are therefore not recommended at this time. Operational research is needed for efficacy and practicability.
6 CHAPTER 3: RULING OUT TB DISEASE BEFORE TB PREVENTIVE TREATMENT Active and systemic TB screening to rule out active TB disease among all clients is mandatory before initiating TB preventive treatment. Initiating TPT to a client with active TB can lead to the delay of TB disease development and therefore favour the development of drug resistance if TB disease is not picked and correctly treated. Therefore, excluding active TB disease before initiating TPT is a critical step in the pathway of providing preventive services to TB risk populations7,8. This chapter recommends approved algorithms for diagnosing TB infection before providing preventive treatment among various key population groups targeted for TPT in Tanzania.
3.1 Targeted populations at high risk of contracting TB disease
3.1.1 People living with HIV
• Infants < 12 months • Children > 12 months • Adults and adolescents including pregnant women and breastfeeding mothers • All adults and children living with HIV who completed TB treatment
3.1.2 HIV-negative clients with history of TB contact
• Under five years household contacts of bacteriological confirmed TB patients. • Individuals aged five years and above who are household contacts of bacteriologically confirmed TB patients. • High-risk household contacts of patients with multidrug-resistant tuberculosis
3.1.3 Other at-risk population groups
• PWUDs • Prisoners • Miners
7 Sabasaba, A., Mwambi, H., Somi, G. et al. Effect of isoniazid preventive therapy on tuberculosis incidence and associated risk factors among HIV infected adults in Tanzania: a retrospective cohort study. BMC Infect Dis 19, 62 (2019). https://doi.org/10.1186/s12879-019-3696-x 8 Pathmanathan I, Ahmedov S, Pevzner E, Anyalechi G, Modi S, Kirking H, Cavanaugh JS. TB preventive therapy for people living with HIV: key considerations for scale-up in resource-limited settings. Int J Tuberc Lung Dis. 2018 Jun 1;22(6):596-605. doi: 10.5588/ijtld.17.0758. PMID: 29862942; PMCID: PMC5989571
7 3.2 Algorithms for ruling out active TB disease among risk population The following algorithms shall be used to rule out active TB disease in each given risk population group. Identification of target population of the specific risk group to be considered for TPT will proactively be undertaken by the health care providers at both health facility and community level.
3.2.1 Algorithm for People living with HIV
3.2.1.1 Infants < 12 months
TB screening policy in Tanzania emphasizes provider-initiated TB screening to all pregnant mothers and immediately after delivery before instituting BCG vaccination. All infants with a history of TB contact should be screened using paediatric TB screening questionnaire (TSQ). If the evaluation shows no TB diseases, the infants should be initiated on TPT.
For those found with presumptive TB, active TB should be ruled out using National standard for diagnosis of TB in infants.
Note: Infants living with HIV who have poor weight gain, fever, irritable or current cough, or who have a history of TB contact, should be evaluated for TB and other diseases that cause such symptoms.
3.2.1.2 Children > 12 months
All children should be screened by using under five years TB screening questionnaire (TSQ) and TB score chart for children as attached in annex 1H. If the evaluation shows no TB disease, the children should be initiated on TPT. For those with presumptive TB, active TB disease should be ruled out by using National standard for diagnosis of TB in Children
3.2.1.3 Adults and adolescents including Pregnant women and
breastfeeding mothers Adults and adolescents including pregnant women and breastfeeding mothers should be screened for TB using TB screening questionnaire (TSQ), as attached in annex 1A and those with no signs and symptoms of TB disease should be initiated on TPT. The resulting presumptive TB cases should be evaluated for active TB and other diseases using National TB diagnostic algorithms.
8 Summary Adults and adolescents living with HIV should be screened for TB according to a clinical algorithm. Summary Those who do not report any of the symptoms of current cough, fever, weight Adults loss and adolescents or night sweats are living withtoHIV unlikely should have be screened active for TB be TB and should according offeredto a clinical treatment, preventive algorithm. regardless of their ART status. Those who Chest radiographydo notmayreport be any of the offered to symptoms people livingof current with HIVcough, and onfever, ARTweight and preventive treatment be given to those with no abnormal radiographic be loss or night sweats are unlikely to have active TB and should offered findings. preventive Adults treatment, regardless and adolescents living with HIVof their whoARTare status. screened for TB according to a Chestalgorithm clinical radiography may be offered to people and who report any of the symptoms living with HIV and of current on ART cough, and fever, preventive treatment be given to those with no abnormal radiographic weight loss or night sweats may have active TB and should be evaluated for findings. TBAdults and adolescents and other diseases that living with cause HIVsymptoms. such who are screened for TB according to a clinical algorithm and who report Stool specimens for Gene-Xpert and urine any of the symptoms for TB urineof current LAM cough, should fever, be weight loss or night sweats may have active considered where other specimens cannot be obtained. TB and should be evaluated for TB and Remark: otherradiography Chest diseases thatshould cause such not be symptoms. a requirement for initiating TB Stool specimens for preventive treatment among PLHIVGene-Xpert and urine for TB urine LAM should be considered where other specimens cannot be obtained. Remark: Chest radiography should not be a requirement for initiating TB preventive treatment among PLHIV
Figure 1: Algorithm for ruling out TB; for children above 12 months, Adult and adolescent including pregnant women and breastfeeding mothers living with HIV.
9 considered where other specimens cannot be obtained. Remark: Chest radiography should not be a requirement for initiating TB preventive treatment among PLHIV
3.2.2 Algorithm for HIV negative clients
3.2.2.1 Under five years contact of bacteriological confirmed
TB patient All under five years with known contact with bacteriologically confirmed PTB patients should be screened by using TB screening questionnaire (TSQ) as attached in annex 1A. Children found with no presumptive TB should be initiated on TPT. Active TB disease should be ruled out in those presumptive TB cases by using National guidelines.
3.2.2.2 Other at-risk groups
TPT is recommended to other risk groups, including individuals aged 5 years and above who are household contacts of bacteriologically confirmed TB patients including those with multidrug-resistant tuberculosis, PWUDs, prisoners and miners. They should be screened for TB by using TB screening questionnaire (TSQ) as attached in annexes 1. Those who are found with presumptive TB, should further be investigated to rule out active TB by using the National algorithm for diagnosis of TB. Individuals with no signs and symptoms of TB disease, and all presumptive TB cases who are found to have no active TB disease after further TB investigation should be tested for TB infection using TST/IGRA/TBST, and those tested positive should be evaluated for initiation of TPT. The algorithm for ruling out TB among other risk groups is shown in figure 2 below.
Figure 2: Algorithm for ruling out active Tuberculosis among other
risk groups.
10 Note: a. Any symptom of TB: cough, haemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, fatigue b. Clients for whom TBI treatment is not indicated should be given information about TB, including the importance of seeking care if symptoms of TB develop. NB Chest X Ray (CXR) would be offered whenever available, but TPT must not be deferred in their absence
3.3 Tests for TB infection
The country will adopt WHO recommended methods for TBI testing, which are Tuberculin skin test (TST) and Interferon Gamma release assay (IGRA), which will be placed at lower-level health facilities and hospitals respectively, depending on their availability.
3.3.1 Interferon-Gamma Release Assay (IGRAs)
The Interferon-Gamma Release test (IGRAs) is an enzyme-linked immunosorbent test for the quantitative measurement of interferon gamma (IFN) in human whole blood that is stimulated in vitro by the antigen from the bacteria Mycobacterium tuberculosis. It is meant to be used as a tool to help in TB infection diagnosis.
Because the test will continue to be positive after therapy is finished,
IGRAs should not be used to track the effectiveness of TB preventive treatment. Three to nine weeks are needed for the test to incubate. After 8–10 weeks, a negative test needs to be done again.
3.3.2 The Mantoux tuberculin skin test (TST)
The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis by reading induration reaction 48-72 hours after an intradermal injection of the purified protein derivative (PPD) of Mycobacterium tuberculosis.
Most persons can receive a TST without any problem. It is contraindicated
only for persons who have had a severe reaction (such as necrosis, blistering, anaphylactic shock, or ulcerations) to previous TST. It is not contraindicated even among infants, children, pregnant women, persons who are HIV-infected, or persons who have been vaccinated with BCG though the interpretation of the results will differ.
11 3.3.3 Mycobacterium tuberculosis antigen-based skin tests (TBSTs) These are the new tests for the diagnosis of Tuberculosis infections. The TBST class is defined as skin tests for the detection of TB infection that use MTB specific antigens (ESAT6 and CFP10)9. TBST is an acceptable alternative to TST and IGRA and it can be used in urban and rural settings.
There are three TBSTs tests:
• C-TB (Serum Institute of India, India) • C-TST (formerly known as ESAT6-CFP10 test, Anhui Zhifei Longcom, China) • Diaskintest (Generium, Russian Federation)
These tests have similar specificity to IGRA and more superior to TST to all group categories and should be used once available.
Note: 1. The groups to be tested for TB infection should include individuals above 5 years household contacts of bacteriological confirmed TB patients, prisoners, PWUDs, and miners 2. IGRA and TST are not a requirement before initiating TPT in PLHIV or for children less than five years who are a contact of a person with bacteriologically confirmed PTB disease. 3. Immune response to TB antigens varies among people, and TST and IGRA could remain positive even after successful completion of TPT. Therefore, the results of TST and IGRA should not be used to assess the efficacy of TPT. 4. Overall, testing with TST or IGRA should not be considered a mandatory requirement for initiating TPT (especially where access to testing services remains very limited) given that the benefits of treatment (without testing) still outweigh the risks. It may be done as a part of eligibility screening where feasible. 5. These tests may provide a false negative result, particularly among immunocompromised hosts who are at a greater risk for severe forms of disease and death if they develop TB.
9 WHO consolidated guidelines on tuberculosis 2022: module 3: diagnosis: tests for TB infection
12 CHAPTER 4: TUBERCULOSIS PREVENTIVE TREATMENT
4.1 Definition and rationale for TPT
After contracting Mycobacterium tuberculosis, people who are thought to be at risk for developing TB disease are given medication in an effort to lower that risk. This treatment is known as TB preventive treatment (TPT). It was formerly known as Latent TB Infection (LTBI) treatment. Based on the underlying epidemiology and burden of TB, the provision of TPT is based on the likelihood that the condition in particular risk groups will proceed to an active TB disease. Due to the burden on resources required to care for the sick people, this will have a negative influence on the community’s economic situation.
4.2 Benefits of provision of TPT
4.2.1 Population level benefits
• Decreases TB incidence. • Reduces the risk of new infections in the community • Maximizes productivity of individuals in National socioeconomic development.
4.2.2 Individual benefits
• Prevents progression of TB infection to active TB disease in exposed individuals including household contacts of bacteriologically confirmed TB patients. • Prevents deaths especially among PLHIV as TB is the leading cause of death. Increases survival of PLHIV even when they are on ART. Provides additional protection when given immediately after completion of TB treatment among PLHIV. • Prevents post TB lung disease and its associated mortality which could result from active TB disease complications. Post TB lung disease occurs in up to 50 % of TB patients and it is associated with increased mortality. • Saves families from catastrophic costs of having active TB disease; almost 20% of household income is spent to manage TB patient.
13 4.3 Eligibility criteria for provision of TPT Exclusion of active TB is critically important before TB preventive treatment is started. Rifapentine plus isoniazid (3HP) is given weekly for three months for those aged 15 years and above, while rifampicin plus isoniazid (3HR) is given daily for three months to those <15 years of age. Isoniazid daily for six months is given as an alternative regimen to all clients not fit for 3HP and 3HR. This treatment requires consideration of several steps, including identification of HIV-positive clients, under five household contacts of bacteriologically confirmed patients and other at- risk groups, screening in order to exclude active TB, assessing eligibility for TPT, starting TPT and monitoring of treatment adherence and side effects.
A. For people with no history of TB treatment
All HIV positive individuals who screen negative for active TB according to the TSQ are eligible for TPT. Under-five household contacts of bacteriologically confirmed TB patients screened negative according to the TSQ for children should also receive TPT. Other at-risk groups (household contacts aged ≥ 5 years of bacteriologically confirmed TB patients, prisoners, PWUDs, and miners) should receive TPT after confirmation of TBI by either TST, IGRAs or TBST.
B. For people with history of TB treatment
People living with HIV who successfully complete their TB treatment should immediately receive a course of TPT. It has been shown that PLHIV who receive TPT immediately after completion of TB treatment have less risk of TB recurrence and mortality.
C. Exclusion criteria for TPT include
• Alcohol abuse • Terminal ill WHO stage IV clients • Non-adherence to long term treatment • Current or past history of hepatitis • Medical contraindication to TPT medications/drug
D. TPT should only be offered in the following situations:
• Where quality supportive counselling is available after effective screening for active TB. • Where there is capacity for follow-up and monitoring of patients to encourage adherence to preventive treatment. • Where there is capacity to manage side effects and exclude active TB during TPT.
14 4.4 Recommended TPT regimens
The following are TB preventive treatment regimens recommended for
use in Tanzania. i. Three months of isoniazid plus rifapentine weekly (3HP) ii. Three months of isoniazid plus rifampicin daily (3HR) iii. Isoniazid monotherapy for 6 months (6H) - alternative TPT regimen to those contraindicated to 3HP and 3HR
4.4.1 Three months of weekly isoniazid plus rifapentine (3HP)
Isoniazid plus rifapentine weekly for 3 months (3HP) has shown to have similar efficacy as that of IPT daily for 6 months for TB prevention. A FDC tablet of rifapentine 300 mg/isoniazid 300 mg is available and reduces the pill burden substantially. This regimen can be used by all categories of eligible individuals aged ≥15 years until appropriate paediatric formulations are available in Tanzania.
4.4.2 Three months of daily isoniazid plus rifampicin (3HR)
Dispersible FDC formulations of isoniazid plus rifampicin daily for 3 months (3HR) regimen provide a better tolerated and child-friendly option compared to isoniazid. This TPT regimen can be used for children aged between 0 and 14 years. Child-friendly FDCs of RH have the added benefit of already being in the National supply chain for treatment of children <25 kg. Caution should be used in children on ART regimens containing a boosted protease inhibitor (PI) or integrase strand transfer inhibitors (INSTIs) due to drug-drug interactions between Rifamycins and these ARVs.
4.4.3 Six months of daily isoniazid monotherapy (6H)
Tanzania has been using isoniazid preventive treatment (IPT) as TPT in the past in PLHIV and children aged below five years who are contacts of bacteriologically confirmed TB patients. Isoniazid monotherapy daily for 6 months continues to be an alternative TPT regimen of choice particularly to those contraindicated to 3HP and 3HR. Isoniazid is the preferred regimen among HIV infected children on protease inhibitor-based regimen (lopinavir–ritonavir), nevirapine, or integrase inhibitors due to potential drug–drug interactions with other regimens.
15 Table 1: Characteristics of available TPT regimens (Source WHO Operational Handbook on tuberculosis: Module 1: Prevention) 3HP 3HR 6H
dose (total number of pills 3 FDCs/Weekly 3 FDCs/Daily 1/Daily for average adult) a
All ages: child-friendly (dispersible) All ages; child-friendly formulation ≥ 2 years; no child- (dispersible) available; Children friendly formulation formulation available preferred in available and recommended up HIV+ to 25 kg weight children on LPV- RTV, or NVP
Pregnant Not known Safe for usec,d Safe for usec
women
Contraindicated:
All PIs, NVP/most
Contraindicated: NNRTIs All PIs, NVP/ Interactions NNRTIs, TAF Use with caution: TAF No restriction with ARTb Use: Adjust dose:
TDF, EFV (400 mg), DTG, RAL
DTG,e RALe Use:
TDF, EFV (400 mg)
16 Flu-like syndrome, Hypersensitivity hypersensitivity Hepatotoxicity reactions, Flu-like reactions, syndrome, Hypersensitivity (more), hepatotoxicity (less),Hepatotoxicity hypersensitivity reactions, peripheral gastrointestinal (GI) rash, GI upset, (more), Toxicity reactions, hepatotoxicity (less), neuropathy, upset, orange peripheral gastrointestinal (GI) rash, GI upset, rash, Toxicity discoloration of body hypoprothrombinemia, neuropathy, upset, orange fluids, orange discoloration ofrash, discoloration of rash, body hypoprothrombinemia, GI upset hepatotoxicity (less) body fluids orange discoloration of fluids, rash, GI upset hepatotoxicity (less) body fluids Best absorbed on Best Oral rifapentine an absorbed empty on Oral rifapentine bioavailability is 70% an empty Rifampicin absorption stomach; up bioavailability (not HP); is peak 70% Rifampicin is rapid butabsorption may bestomach; to up50% Absorption (not HP); peak isdelayed rapid but may be to reduction 50% in Absorption concentration or decreased concentration increased if given delayed or meals by high-fat decreased reduction peak in increased with a meal if given by high-fat meals peak concentration with a meal concentration with a fatty with a fatty meal meal
Note: Note: DTG=dolutegravir, DTG=dolutegravir, EFV=efavirenz, EFV=efavirenz, H=Isoniazid, LPV–RTV=lopinavir-ritonavir, H=Isoniazid, LPV–RTV=lopinavir-ritonavir, NNRTI=non-nucleoside NNRTI=non-nucleosidereverse reverse transcriptase inhibitors,NVP=nevirapine, transcriptase inhibitors, NVP=nevirapine, P=rifapentine, P=rifapentine, PIs=protease PIs=proteaseinhibitors, inhibitors, R=rifampicin, RAL=raltegravir, TAF= R=rifampicin, RAL=raltegravir, TAF=tenofovir tenofoviralafenamide, alafenamide, TDF=tenofovir TDF=tenofovir disoproxil disoproxilfumarate fumarate a. a.Average Averageavailable availableadult adultformulations formulations b. For women living with b. For women living with HIV (as HIV (as well well as as HIV-negative) HIV-negative)receiving receivingrifamycin-based rifamycin-based TPTTPT andandoral oralcontraceptives, contraceptives, consider consider additional additional barrier barriercontraception contraception methods methodsto to prevent pregnancy. prevent pregnancy. c. One randomized trial has shown increased risk of poor birth outcomes for mothers c. One randomized trial has shown increased risk of poor birth outcomes for mothers taking isoniazid during pregnancy; however, several other studies have shown taking isoniazid during pregnancy; however, several other studies have shown benefits of IPT; hence caution is required. benefits of IPT; hence caution is required. d. Bleeding attributed to hypoprothrombinaemia has been reported in infants and d. Bleeding mothersattributed following tothehypoprothrombinaemia use of rifampicin in has late been reported pregnancy. in infants Vitamin K isand mothers following the use of rifampicin in late pregnancy. recommended for both the mother and the infant postpartum if rifampicin is used Vitamin K is recommended in the last few for bothofthe weeks mother (FDA). pregnancy and the infant postpartum if rifampicin is used in the last few weeks of pregnancy (FDA). e. Indicates that drug interaction has been studied in adults and not children; applies e. Indicates to adultsthat drug taking DTGinteraction has been studied in adults and not children; applies or RAL only. to adults taking DTG or RAL only.
17 Table 2: Recommended Regimens for TPT
Population Preferred Regimen Caution Alternative
age group Regimen
0-14 years Daily isoniazid Plus CLHIV on PI based Isoniazid
rifampicin for three ART regimen monotherapy months (3HR) cannot use 3HR daily for 6 months (6H) Contraindicated:
All PIs, NVP/most
NNRTIs
Use with caution:
TAF
Adjust dose:
DTG, RAL
Use:
TDF, EFV (400 mg)
Table 3: Recommended dosage for TPT
Dose per kg body Maximum daily
Drug regimen Population weight per day dose Number of tablets Three months of for body weight Isoniazid + rifapentine rifapentine plus more than 30 kg ≥ 15 years fixed dose combination isoniazid (3HP) Isoniazid: 900mg (300 mg/300 mg) weekly Rifapentine: 900mg 3 Rifampicin: 15 mg Children < 10 (range 10-20 mg) Daily isoniazid Plus Rifampicin: 600mg years Isoniazid: 10 mg rifampicin for three Isoniazid: 300 mg (range7-15 mg) months (3HR) Children ≥ 10 Rifampicin: 10 mg years Isoniazid 5 mg Isoniazid alone, daily All population Children 5mg 300 mg for 6 months (6H) groups Adult 10 mg (range, 7–15 mg)
Note: For Weight and Age Based Dosing Charts: Refer Annex 2
18 4.4.4 Pyridoxine and TPT Pyridoxine (B6): One of the undesirable side-effects of long-term treatment with high-dose isoniazid is peripheral neuropathy that develops secondary to a deficiency of vitamin B6 (pyridoxine) during therapy. Individuals at risk for peripheral neuropathy, such as those with malnutrition, chronic alcohol dependence, renal failure or diabetes, or who are pregnant or breastfeeding, should receive vitamin B6 supplements when taking isoniazid-containing regimen. Additionally, pregnant and postpartum women and exclusively breastfed infants should receive vitamin B6 while taking isoniazid. The standard dose of pyridoxine when used prophylactically for prevention of neuropathy among patients taking isoniazid is 10–25 mg/day. Peripheral neuropathy occurs infrequently among other patients taking standard doses of isoniazid, which is easily recognized (as symmetrical numbness and tingling of the extremities) and usually easily reversible upon withdrawal of isoniazid and institution of high-dose pyridoxine therapy (100–200 mg/day). Therefore, routine pyridoxine supplementation with isoniazid is probably not necessary and its absence should not become a barrier to TPT initiation.
4.5 Management of close contacts of a drug-resistant tuberculosis
patient Contacts of DR-TB are people who share the same household or spend prolonged hours of a day together with a DR-TB patient in the same indoor settings. The following are recommendations for management of close contacts of DR-TB patients: • Should be provided with information and health education on DR- TB disease. • Should undergo a TB symptom screening which includes (cough, weight loss, excessive night sweats, fever and haemoptysis). • All close contacts who have signs and symptoms of TB should be investigated for TB disease. • Close contacts who do not have signs and symptoms of TB should undergo: • clinical monitoring and assessment to rule out active TB • follow up clinical assessment
Note: For more clarification of management of contacts of DR-TB patients,
please refer to DR-TB management guidelines.
19 4.6 Future development in TPT These guidelines will provide a room to take up new innovations and new drug regimens and also vaccine in accordance to The National commodities and technologies Transition guideline 2022 and as per the Global plan to end TB.
4.7 Drug-Drug Interactions with Antiretroviral
4.7.1 Rifamycins and ARVs
Rifamycins interact with a number of ARVs used in Tanzania including NNRTIs, PI and INSTIs. When Rifamycins are used with these ARVs, they induce a group of liver enzymes (Cytochrome P450) which increase the metabolism of the co-administered ARVs with consequent reduction of their therapeutic levels. In such situations, the dose of ARVs should be increased and if the concentration of ARVs becomes so low it should not be co-administered with Rifamycins as shown in table 4 and 5A.
4.7.2 Rifamycins and other Medication
Rifamycins also interact with other medicines as summarized in table 5B. Sound clinical judgement is therefore required when these medicines are to be co-administered with Rifamycin-based TPT, either by avoiding these regimens or adjusting the dose of other co-administered drugs).
20 Key points: Key points: • Coadministration of commonly used ARVs with TPT is safe, and alternatives are • Coadministration of commonly used ARVs with TPT is safe, and alternatives are available when low ARV exposure is suspected due to drug–drug interaction. available when low ARV exposure is suspected due to drug–drug interaction. • Caution is required when an individual receiving TPT is also on treatment for other • Caution is required when an individual receiving TPT is also on treatment for other comorbidities. comorbidities. • Women on hormonal contraceptives should use an additional barrier contraceptive • Women on hormonal contraceptives should use an additional barrier contraceptive to avoid pregnancy when using rifamycin-based TPT. to avoid pregnancy when using rifamycin-based TPT.
Table 4: Drug-drug interactions between Rifamycin based TPT and ARVs
Table 4: Drug-drug interactions between Rifamycin based TPT and ARVs Name of ARV Type of interaction Recommended action Name of ARV Type of interaction Recommended action TDF No Interaction No dose adjustment TDF No Interaction No dose adjustment 3TC/FTC No interaction No dose adjustment 3TC/FTC No interaction No dose adjustment EFV Reduced concentration No dose adjustment EFV Reduced concentration No dose adjustment NVP Reduced concentration Don’t use NVP Reduced concentration Don’t use DTG Reduced concentration Double the dose (50mg) and administer DTG Reduced concentration Double the dose (50mg) and administer in 2 divided doses 12 hourly apart when in 2 divided doses 12 hourly apart when using 3HR as TPT using 3HR as TPT No dose adjustment required when using No dose adjustment required when using 3HP 3HP pDTG Reduced concentration Double the dose and administer in 2 pDTG Reduced concentration Double the dose and administer in 2 divided doses 12 hourly apart when using divided doses 12 hourly apart when using 3HR 3HR No dose adjustment when using 3HP No dose adjustment when using 3HP AZT No interactions No dose adjustment AZT No interactions No dose adjustment ATV/r Reduced concentration Don’t use ATV/r Reduced concentration Don’t use LPV/r Reduced concentration Double the dose to 800mg/200mg LPV/r Reduced concentration Double the dose to 800mg/200mg RTV Reduced concentration Don’t use RTV Reduced concentration Don’t use ABC No interaction No dose adjustment ABC No interaction No dose adjustment RAL Reduced concentration Double the dose to 800mg RAL Reduced concentration Double the dose to 800mg DRV/r No studies Don’t use DRV/r No studies Don’t use
21 Table 5A: Drug-drug interactions between Rifamycin based TPT and available ART regimens in Tanzania
ART Regimen Type of interaction Recommended action
1st Line regimen (Paediatric)
ABC+3TC +pDTG/DTG Reduced concentration of DTG If <20Kg, double* the dose of pDTG AZT + 3TC + DTG If above 20Kg double* the dose of DTG 50mg *One dose in the morning and one dose in the evening TDF+3TC+DTG Reduced concentration of DTG Double the dose to 50mg bid when using 3HR No dose adjustment when using 3HP ABC/3TC+LPV/r Reduced concentration of Double the dose of AZT/3TC+LPV/r LPV/r LPV/r 2nd Line regimen (Paediatric) AZT/3TC+LPV/r Reduced concentration of Double the dose of ABC+3TC+LPV/r LPV/r LPV/r TDF+3TC+DTG Reduced concentration of DTG If <20Kg, double* the dose of pDTG AZT+3TC+DTG If above 20Kg double* the dose of DTG 50mg when using 3HR No dose adjustment when using 3HP *One dose in the morning and one dose in the evening 3rd Line regimen (Paediatric) pDTG+DRV+RTV+AZT+3TC No studies Don’t use DTG+DRV+RTV+AZT+3TC 1st Line regimen (Adolescents and Adults) TDF +3TC +DTG (TLD) Reduced concentration of DTG Increase the dose of ABC + 3TC+ DTG DTG by 50mg when AZT + 3TC + DTG using 3HR No dose adjustment when using 3HP TDF + 3TC +EFV (TLE400) Reduced concentration No dose adjustment 2nd Line regimen (Adolescents and Adults) AZT/3TC+ATV/r Reduced concentration of Don’t use TDF/FTC+ATV/r ATV/r AZT/3TC+LPV/r Reduced concentration of Double the dose to LPV/r 800mg/200mg 3rd Line regimen (Adolescents and Adults) DTG + DRV/r + AZT/3TC No studies Don’t use DTG (BD) + LPV/r + (AZT/3TC Reduced concentration of DTG Double the dose to or TDF/FTC) Reduced concentration of 800mg/200mg LPV/r DTG+ATV/r+ AZT/3TC Reduced concentration of Don’t use ATV/r
Table 5B: Drug-drug interactions between Rifamycin based TPT and other medications 22 Drug-drug Drugs Effects or TDF/FTC) Reduced concentration of 800mg/200mg LPV/r DTG+ATV/r+ AZT/3TC Reduced concentration of Don’t use ATV/r
Table 5B: Drug-drug interactions between Rifamycin based TPT and other medications
sulfasalazine, tacrolimus, theophylline, antibiotics concentration by (such as chloramphenicol, clarithromycin, speeding up dapsone, doxycycline, linezolid, telithromycin), clearance quinolones (such as ciprofloxacin), antiarrhythmics (such as disopyramide, mexiletine, quinidine), certain antimalarial drugs (such as atovaquone, quinine), anti-seizure drugs (such as phenytoin, phenobarbital, lamotrigine), azole antifungals (such as itraconazole, ketoconazole, voriconazole), benzodiazepines (such as midazolam), "blood thinners" (such as warfarin), calcium channel blockers (such as diltiazem, nimodipine, verapamil), certain anti- cancer drugs (such as imatinib, irinotecan), certain oral drugs for diabetes (such as repaglinide), certain hormone replacement drugs (including estrogens such as conjugated estrogen, progestins such as medroxyprogesterone), certain drugs for mental/mood disorders (including clozapine, haloperidol, tricyclic antidepressants such as amitriptyline), opioid pain relievers (such as methadone), and certain drugs for sleep (such as ramelteon, eszopiclone, zopiclone).
23 4.8 Adverse Reactions, Monitoring and Management
4.8.1 Adverse reactions to TPT drugs
Although minor side effects may occur commonly, however serious events leading to death or requiring withdrawal of TPT are rare. It is important to identify any sign of drug toxicity early on and manage it promptly. Adverse reactions by harming the individual, impacts negatively on adherence, completion and reputation of the program. A thorough history and medical examination are required in the identification and grading of adverse reactions. Health Care providers should fill yellow forms (ADR forms) and send them to Tanzania Medicine and Medical Devices Authority (TMDA). a. Rifampicin i. Gastrointestinal symptoms, such as nausea, anorexia and abdominal pain, are rarely severe enough to discontinue treatment. ii. Hepatotoxicity, evidenced by transient asymptomatic hyperbilirubinemia, may occur in 0.6% of persons taking rifampicin. Hepatitis is more likely when rifampicin is combined with isoniazid. iii. Cutaneous reactions, such as pruritis (with or without a rash), may occur in about 6% of persons taking rifampicin. These are generally self-limiting and may not be a true hypersensitivity; and continued treatment may be possible. iv. Rifamycin hypersensitivity syndrome is rare, associated mainly with intermittent use of high dose of Rifamycins. It generally develops after three to six months of treatment. Clinical features include hypotension, nephritis or thrombocytopenia manifested by symptoms such as fever, headache, dizziness/light-headedness, musculoskeletal pain, petechiae and pruritis. v. Orange discoloration of body fluids such as urine and tears is expected and harmless, but persons prescribed Rifamycins should be advised beforehand.
24 b. Rifapentine i. Among TPT drugs, Rifapentine is relatively safe, well tolerated even among individuals with hepatic dysfunction. Clinically significant adverse drug reactions are mostly flu-like, often mild and self-limiting, occurring in up to 3.5% of individuals receiving 3HP. Severe 3HP induced adverse reactions such as hypersensitivity and hypotension are uncommon and resolve after stopping 3HP without long term effects. Like rifampicin, rifapentine also causes change in the colour of body fluids to orange- red. GIT symptoms such as nausea and vomiting may also occur. Other rare features include pancytopenia and pruritus.
c. Isoniazid monotherapy i. Elevation of serum liver enzymes (transaminases) concentrations occurs in 10-20% of people on isoniazid. In most cases elevation of transaminases is asymptomatic and self-limiting requiring no intervention. Isoniazid should be stopped/discontinued if transaminases exceed threefold the upper limit of normal and symptoms develop or fivefold regardless of the absence of symptoms. ii. Hepatitis: Clinically significant hepatitis induced by isoniazid is rare, occurring in 0.1% of people on isoniazid. However, concurrent use of hepatotoxic drugs or co-existence of hepatotoxic risk factors such as alcohol abuse and older age >65years increase the risk of developing hepatitis. Although hepatitis is uncommon among young people <20 years, isoniazid induced hepatitis may develop in this age group in the presence of underlying risk factors for liver disease. Therefore, monitoring for clinical hepatitis should be done for all age groups on isoniazid. iii. Peripheral neuropathy among individuals without underlying medical conditions associated with peripheral neuropathy such as diabetes mellitus, malnutrition, HIV, chronic kidney diseases, alcoholism or concurrent use of neuropathy inducing drugs such as statins, isoniazid induced peripheral neuropathy is uncommon occurring in 0.2% in people on isoniazid. However, in people with other risk factors as outlined above the rate of peripheral neuropathy ranges between 2% to 44% (Jones et al 2020, Current clinical pharmacology). In this patient group, routine pyridoxine (Vitamin B6) supplementation is recommended. iv. Pellagra: Isoniazid can cause pellagra through interruption of endogenous production of niacin (vitamin B3) in persons with underlying nutritional deficiency and alcoholism. Clinical presentations include diarrheoa, dementia and dermatitis with a Casal’s necklace.
25 4.8.2 Management of adverse events Adverse events during TPT must be minimized and promptly managed. If a severe adverse event is encountered, TPT must be immediately discontinued, and supportive medical care provided. Conservative management and continuation under observation can be considered in the presence of mild to moderate adverse events as determined by the healthcare provider. Potential adverse events and their management approaches are indicated in table 6 below:
26 Table 6: Management of potential adverse reactions following treatment with TPT Adverse event Stop and consider Stop and do not reintroduce reintroduction with caution
Flu-like syndrome (attacks) If mild and not increasing If moderate to severe symptoms, of fever, chills and malaise, continue treatment and consider alternative TPT options sometimes with headache, observe closely without a rifamycin (6H) dizziness or bone pain
Drug-associated fever only Consider reintroduction if If fever more than 39⁰C after the fever settles below 39⁰C, previous episode of drug – but stop permanently if associated fever fever recurs Persistent nausea, frequent Administer antiemetic or If there is nausea, vomiting or vomiting and/or persistent anti-diarrheoal medication diarrheoa which requires episodes of unformed and consider aggressive rehydration reintroducing TPT with watery stools caution once the symptoms have resolved Cutaneous reactions Diffuse rash (no vesicles) If there are extensive bullous Diffuse rash with limited lesions/ulceration of mucous vesicles membranes/Stevens Johnson or toxic epidermal necrolysis, contact a specialist and use steroids
Other hypersensitivity Assess the clinical
reactions (hypotension, severity of the symptoms acute bronchospasm, and if severe consider alternative TPT options conjunctivitis, without a rifamycin (6H) thrombocytopenia)
Hepatitis (early symptoms ALT/AST < 5 times upper ALT/AST ≥5 times the upper limit of of weakness, fatigue, loss limits of normal and normal in the absence of symptoms of appetite, persistent absence of symptoms ALT/AST ≥3 times the upper limit of nausea) normal in the presence of symptoms.
Psychosis Psychiatric evaluation, Attributable to Isoniazid
antipsychotic therapy Seizures Withhold isoniazid Attributable to Isoniazid pending resolution of seizures, evaluate possible causes of seizures.
Key point: Liver function tests (LFTs) prior to initiating TPT are not routinely indicated. Baseline and follow-up LFTs are only needed when there is a defined risk, such as pre-existing liver dysfunction, liver cirrhosis or other indications.
27 4.9 Pharmacovigilance and Surveillance of TPT Drug Adverse Reactions Pharmacovigilance activities are coordinated by TMDA and its’ systems have been in place since 1993. The spontaneous reporting is the most common ADR reporting method in Tanzania and special forms (Yellow Forms) have been developed to help collect adverse drug reactions data from all patients including new medicines, regimens, or new testing protocols. In addition, the use of new medicines will require the utilization of active drug safety monitoring and management (aDSM). Healthcare workers will be required to report actively all serious adverse events and adverse events of specially interest.
Adverse effects, including those considered as medically “minor”, may
be a barrier for adherence in a person who is otherwise well. TPT related adverse reactions (ADRs), identified during the course of treatment should be properly monitored, managed and reported per National recommendation, using National (TMDA) reporting systems.
4.9.1 Aim of Pharmacovigilance
• To identify and quantify new adverse drug reactions (ADRs) • To identify risk factors and populations at risk • To detect increase in frequency of known ADRs • To detect drug interactions • To monitor benefit-risk profile of medicines and ensure that they remain within acceptable bounds ADR profile of medicines within therapeutic class • To contribute to good clinical practice in pharmacotherapy • To prevent patients from unnecessary harm
4.9.2 Reporting ADRs
The spontaneous reporting method will be used for reporting TPT drug ADRs in Tanzania and special forms (Yellow Forms) have been developed to help collect adverse drug reactions data from all patients including new medicines, regimens, or new testing protocols.
4.9.3 Modalities of reporting in passive method
The following forms/tool are used to document and or report ADRs;
• Yellow form (for reporting ADRs to medicines or vaccines) • Green form (for reporting ADRs by patients themselves) • Blue form (for reporting poor quality products) • Pink card (Patient ADR alert card) • PV Register (For recording details on filled forms)
28 The tools are also available in electronic version for ADR reporting; (android, computer and toll-free number): • SQRT: https://sqrt.tmda.go.tz/ • USSD text number: No. *152*00# • Toll free Hotline No.: 0800110084
4.9.4 What to report
• Any undesirable adverse event suspected to be associated with use of; TPT drugs (3HR, 3HP, 6H). • Report all events: expected or not, minor or serious ADR, increase in frequency or severity of known ADR, overdose, abuse, medication errors, lack of efficacy, quality defects, poisoning and ADR associated with medicines withdrawal.
4.9.5 Who should report
Health care providers, Marketing Authorization Holders Manufacturers, patients/clients and the general public should provide reports of any case of suspected ADRs when encountered.
4.9.6 When to report
ADRs should be reported within 24 hours after occurrence and the forms should be filled before the person leaves the facility. Fatal ADRs should be reported immediately.
4.9.7 Where to submit report
i. TMDA headquarters office ii. TMDA website (http://www.tmda.or.tz or via email [email protected] or through fax) iii. TMDA zonal offices iv. Zonal pharmacovigilance centers. v. Regional Medical Officer’s office vi. District Medical Officer’s office vii. In-charge of the Regional and District Hospitals viii. In-charge of the health centers ix. In-charge of the dispensaries x. Superintendent of the Community Pharmacies xi. Superintendent of the Private Health facilities
Note: The forms will be provided free of charge by TMDA and as they are already pre-paid, reporters will not be charged for postal mailing.
29 30 CHAPTER FIVE: ADHERENCE AND ETHICAL CONSIDERATIONS
5.1 Adherence Adherence means sticking firmly to treatment regimen by taking the right medicine, with the right dose, at the right time, in the right frequency, in the right way and exactly as agreed between healthcare providers, clients and care givers. Adherence to the TPT doses throughout the course and treatment completion is important determinants of clinical benefit, both at individual and population levels. Irregular or inadequate treatment reduces the protective efficacy of TPT regimen. Poor adherence or early cessation of TPT can potentially increase the risk of the individual developing TB disease including drug-resistant TB, and hence jeopardizing efforts to stop TB transmission.
Total number of doses taken is a key determinant of the extent of TB
prevention. Success of the TPT strategy is based on adherence to the treatment. As expected, shorter regimens are associated with better adherence and higher treatment completion rates.
5.2 Factors that influence adherence of TPT among all eligible
clients. • Client’s self-commitment. • Client’s ability to fit the medication in their daily routine. • Uninterrupted availability of TPT drugs. • Accessibility to TPT services. • Good tolerability to TPT drugs.
5.3 Factors that enhance adherence of TPT among all eligible
clients.
5.3.1 Client related factors
• Understand the benefit of TPT at individual, family and public levels. • Involvement of treatment support or caregiver.
5.3.2 Health system factors
• Uninterrupted supply of TPT drugs. • Availability of health care provider for provision of TBI services in confidential manner and integrated with psycho-social and adherence support counselling.
31 • A defined visit schedule for the whole course of TPT should be provided to clients during initiation of treatment and encourage clients to properly plan facility visits. Provision of TBI services should also align with the client’s visit to the facility for other health services. • Good linkage to community support services such as TB and HIV. • Health education related to the benefits of TBI s0ervices on multiple client encounters. • TPT client cards with Unique Identity number should be used to capture client information, treatment start date, regimen used, scheduled facility visits, reason for initiation of TPT, other underlying medical and social conditions, and reported AEs.
5.3.3 Regimen related factors:
• Use of shorter and fixed dose combination regimens. • Rational drug selection to minimize drug interactions and side effects. • Follow TPT medications requirements. • Timely identification and management of adverse events related to TPT drugs.
5.4 Effective patient-centred approach to promote adherence
Promotion of adherence will require an effective patient centred approach
and healthcare workers will need to: • Conduct effective counselling of the TPT among eligible individuals and their family members. • Develop a personal adherence plan with the support of a family member, caregiver or health worker as per treatment regimen being provided. Give first preference to the family member to be the treatment supporter in consultation with the person. • Use of home-based DOT, counting empty blisters, refill monitoring etc. at the level of treatment supporter to strengthen adherence monitoring. • Engage the TB survivors/champions at the community level to create a peer support group for social support and continuous motivation of TPT eligible persons and their family to adhere and complete treatment as well as report any adverse events in time for resolution.
32 Suggested actions for improving TPT adherence • Address the reason for interruption. • Counsel the person on TPT and treatment supporter on the importance of adherence to treatment. • Review and agree with the person on TPT and treatment supporter about the best way to improve adherence
Note: Refer to chapter six for further details on counselling
5.5 Treatment completion
A number of endpoints are proposed that could be used to trigger a review of persons on TPT and in some instances, changes to treatment. Client on TPT will be regarded as completing treatment if she/he take the minimum required number of doses in the specific time.
Key Note: Treatment completion. A person initiated on TPT who completed at least: • 80% of recommended dose (68/84) consumed within 4 months of planned TPT duration for 3HR. • 90% of recommended dose (11/12) consumed within 4 months of planned TPT duration for 3HP. • 80% of recommended dose (135/ 168) consumed within 9 months of planned TPT duration for 6H. • All client should be given a doses of one monthly and return to facility for refill and assessment .
5.6 Treatment interruption
a) 3HP Weekly schedule of one dose missed: • If the missed dose is remembered within the next 2 days, the person can take the dose immediately. Continue the schedule as originally planned (i.e., continue to take remaining doses following the same schedule). • If the missed dose is remembered more than 2 days later, the person can take the missed dose immediately and change the schedule for weekly intake to the day the missed dose was taken until treatment completion. This will avoid 2 weekly doses being taken less than 4 days apart.
33 More than 1 weekly doses of 3HP missed: • If between 1–3 weekly doses are missed, treatment is continued until all 12 doses are taken, thus prolonging the treatment duration to a maximum of 16 weeks. • If, however, 4 or more weekly doses are missed, offer counseling and restart the full TPT course under DOT. If adherence to a weekly routine is not possible, discontinue 3HP and offer a daily regimen.
b) 3HR and 6H
Less than 2 weeks:
• Resume preventive treatment immediately upon return and add the number of days of missed doses to the total treatment duration. • Do not change the scheduled date of the next follow-up visit but the last follow-up visit will be postponed by the number of extra days to compensate for missed doses.
More than 2 weeks:
• If treatment interruption occurred after more than 80% of the doses (144 of 6H and 72 of 3HR) were taken, no action is required. Continue and complete the remaining treatment as per original plan. • If less than 80% of doses of 6H or 3RH were taken, and the treatment course can still be completed within the expected time for completion, i.e., treatment duration + 33% additional time (that is a total of 239 days for 6H or 120 days for 3HR), no action is required. Continue and complete the remaining treatment as per original plan. If less than 80% of doses of 6H or 3HR were taken, and the treatment course cannot be completed within the expected time for completion, restart the full TPT course.
5.7 Special considerations
A. PLHIV on Multi-month dispensing ART:
• All eligible PLHIV will be offered TPT in alignment to the differentiated care model that allows for close monitoring of TPT adherence and completion. • Health care provider should ensure close monitoring of clients enrolled into TPT at health facilities or community settings working with CHWs/CBHS.
34 • PLHIV using TPT and ART should be educated to return back to health facilities just in case of any symptoms of TB or development of ADRs. • Monthly TB screening will be conducted by community HIV based service providers.
B. Under-five children on TPT
• Counsel caregiver on the importance of completion of the full dose. • Provide a person-friendly schedule for appointments for drug refills (visit to align with family member taking anti-TB drug in the facility). • Healthcare provider to take note of risk factors for poor adherence and attempt to address them: such as long distance/ transport; orphans (especially if the mother has died); past adverse reactions to medicines or primary caregiver being unwell. • If the child is refusing to take medicine; change the food type so as to better mask the taste or place crushed medicines in the centre of solid food that is easy to swallow. • If a child vomits within 30 minutes. ensure that a new dose is given to the child.
5.8 Ethics in TBI services
Health is a right and not a privilege in Tanzania. Medical care and public health are two complementary and interrelated approaches for promoting and protecting health. The concept of human rights in provision of medical care brings together the rights of both clients and health care providers and refers to the application of general human rights principles to the context of medical care. Clinicians, other health-care providers, and decision makers too often do not consider consulting patients/clients regarding the provision of diagnostic and therapeutic interventions.
TBI being asymptomatic and non-contagious, emphasizes the obligation
for human rights considerations in the context of clinical care and public health at large. Delivery of TBI diagnosis, care and treatment to selected population groups should be non-discriminatory, equal to all eligible groups, ensure participation between provider and clients, the system should be designed to respect and protect human rights.
35 5.9 Key implementation aspects in ethical consideration
5.9.1 Raising awareness
NTLP and health facility managers should:
• Inform the public on availability, accessibility and utilization of TBI services to eligible clients. • Communicate reliable information about TBI to eligible clients as defined in the service delivery package and respect right of choices of TPT among clients. • Outline steps to receive complaints related to ethical concerns from clients and communicate these steps to clients and authorities. • Sensitize health-care workers to abide to medical ethics which emphasize on respecting protecting and ensure confidentiality of individual clients. Moreover, actions/penalties related to malpractices and violation of human rights related to TBI services delivery should be defined and communicate to health care providers.
5.9.2 Prerequisites on health care delivery in the context of ethics
In health-care settings for the delivery of TBI services, health-care
providers should:
• Identify all eligible clients for TBI services, offer appropriate
information on benefits, safety and risks of TB preventive treatment, and refer to service delivery point for timely initiation of medication. Treatment should be self-administered. • Ensure services are accessible to all eligible clients without discrimination by age, sex and socioeconomic status. • Assess barriers that may hinder service utilization by eligible clients. These could be physical, financial or otherwise, and provide options for the best interest of the client. • Communicate benefits and risks in culturally and linguistically appropriate language to clients and with sensitivity to gender. • Understand specific needs of eligible population groups and provide services in line with the good standards of clinical practices. • Ensure timely and safe delivery of TBI services, which are integrated with other services including HIV care, RCH services, nutritional assessment, etc.
36 5.9.3 Feedback from clients Demand and supply in delivery of TBI services are necessities in sustaining impact and ultimate prevention of TB incidence in a population. In this regard, this service package requires the health care workers to use designated tools to document and analyze: • Withdrawals related to AEs to inform actions and decisions related to TBI services. • Challenges facing clients in access and use of TBI services. • Socioeconomic enablers and barriers in utilization of TBI services. • Utilization of TBI services by age and sex.
5.9.4 Assessment tool to measure adherence in each visit, the data
captured should be analysed to inform programmatic actions and decisions. • In order to properly follow up of client’s adherence to medication, there will be TBI-01 tool which will have client profile, date of medication, appointments and AEs experience. • This tool will be monitored at every visit to ensure proper adherence.
37 38 CHAPTER 6: COMMUNITY ENGAGEMENT
6.1 Community TB services
Community TB activities involve a range of activities and services deployed to help TB detection, referral and treatment support for people with TB conducted in places other than health care facility premises. These services need to be patient-centered and involving the community. Community health workers are the front liners in the provision of these services working in collaboration with the respective health care facilities and other community stakeholders10.
6.2 Community Right and Gender (CRG) in TPT
The concept of community right and gender will be incorporated while providing TPT services. This is because TB related stigma and discrimination have negative impacts on the health and wellbeing of TBI clients and other at-risk population, creating barriers to service uptake. To improve the provision of TBI services, the health system should: • Implement tools to measure stigma in the health facilities and communities. • Identify focal points in the health facility to work directly with the stigmatized group. • Enhance health care provider(s) participation in stigma reduction through messages and communication. • Involve members of the stigmatized group in the delivery of the interventions to develop empathy, humanize the stigmatized individual and break down stereotypes. • Develop facility-based client coping mechanisms to overcome stigma at the health facility level. • Integrate TBI services with existing community empowerment initiatives. • Screen GBV while providing TBI services and provide appropriate management • Introduce the concept of human rights while providing TBI services.
6.3 Community Led Monitoring (CLM)
Community Led Monitoring (CLM) is defined as “Mechanisms that service users or local communities use to gather, analyse and use information on an ongoing basis to improve access to quality and the impact of services and to hold service providers and decision makers to account”11.
10 National Operational Guide for Community-Based TB and Leprosy interventions 11 National Community, Rights and Gender implementation guide for TB and Leprosy Response 2021.
39 Community-based monitoring is not the same as routine program monitoring. CLM is about equipping them with planning, monitoring, organizing, assertiveness, and advocacy skills to be effective change agents and duty bearers in their respective communities. Such knowledge includes bio-medical, behavioral, and structural barriers to health service delivery; and indicators relevant to their respective CLM mechanism. All principle of CLM will be utilized to improve the provision of TPT in the country. The CLM will: • Holds both government and non-state service providers accountable for responding to intended beneficiaries’ needs. • strengthens community engagement and ownership • fills public health system information gaps; responds to human rights and gender-related barriers • monitors budgets; and prevents stock-out and expiry of commodities
6.3.1 Programmatic Management of TPT (PMTPT) in Community
settings For effective PMTPT uptake in the community, there is a need for robust sensitization, demand creation so as to help improve health seeking behavior. To complement these efforts, the community health workers are an important group to assist in TPT services delivery in the community.
When the CHW/CBHS conducts contact investigation, TBI and TPT
information should be incorporated in all stages of ACF which will involve evaluation for TPT eligibility for those at risk. depending on individuals’ risk whether they have recent exposure to a TB patient, are immune compromised or have any other comorbidities and create TPT demand at the community level.
To increase coverage and minimize additional costs, programs
implementing ACF should integrate TPT and those providing TPT should link eligible individuals for TB diagnosis and treatment services. Additionally, services can be expanded beyond TB contact investigation services when a need for other services is observed. Contacts of HIV+ index clients should be offered HIV counselling and testing, together with systematic TB screening and those found presumed to have TB offered TB investigations.
Household contacts of bacteriologically confirmed TB patients are
identified as at-risk group of both TB infection and TB disease. They have high prevalence of TB infection and incident TB disease may appear in the subsequent 2-5 years post infection12
40 Screening of household contacts has been shown to be a cost-effective method of active TB case finding and it has a very high yield and therefore it should be conducted by all TB programs13. This will give way to early and effective TB treatment and TPT which will lead to improved TB outcome and act as a strategy for community infection control. This has health and financial benefits to the whole household/family therefore reducing catastrophic health costs resulting from loss of income and healthcare costs. During the period in which the TB patient is receiving TB treatment and care, TPT should be provided to all family members eligible for the service in order to realize the impact of TPT and making interventions such as home visits cost-effective14
Family-centered approach: Means working with TB, HIV patients and
their families in the course of their treatment and prevention services to better understand their experiences in care and assist them to decide on which strategies will best help improve their TPT uptake services. It creates the best environment for TB patients and their household contact with or without TBI.
6.3.2 Role and responsibilities of Community Health Workers
• Community sensitization on TPT and TBI. • Community TB screening and sputum sample referral to rule out active TB. • Community mobilization of target and high-risk populations for TPT. • Conduct ACF among TB contacts of the TB index patients and screening for TBI eligibility and tracing those lost to follow up. • Encourage household contacts of TB patients on the importance of TPT for protection of other family members. • Connect with TB patients and those with TBI more frequently for continued counselling and adherence to TB treatment and TPT and other comorbidities e.g., HIV/AIDS • Monitor TB treatment and TPT adverse drug events and symptom resolution and referrals. • CHW programs should make TPT a routine part of their services, ensure data collection and counselling of patients and those with TBI regarding the importance of TPT.
11 WHO operational handbook on tuberculosis. Module 1: prevention - tuberculosis preventive treatment. Geneva: World Health Organization; 2020. License: CC BY-NC-SA 3.0 IGO. 12 Lung T, Marks GB, Nhung NV, Anh NT, Hoa NLP, Anh LTN, et al. Household contact investigation for the detection of tuberculosis in Vietnam: economic evaluation of a cluster-randomized trial. Lancet Glob Health. 2019;7(3):e376–84 14 WHO operational handbook on tuberculosis. Module 1: prevention - tuberculosis preventive treatment. Geneva: World Health Organization; 2020. License: CC BY-NC-SA 3.0 IGO.
41 6.3.3 Role and responsibilities of Facility Health Care Workers • Provision of health education on TBI and TPT to the patients and the community to increase awareness and uptake of TPT services. • Screen all at risk groups for TPT eligibility. • Capacity building other healthcare workers. • Integrate TB, HIV services with other services for comorbidities. • Systematic implementation of identification of TB contacts and screening eligibility for TPT through: Mapping out all index TB clients and target population to assist their contact tracing and investigation for TB and TPT. Perform diagnostic services to help rule out active TB among contacts of the index TB patients. • Provide TPT recommended regimens to all eligible individuals who have been identified. • Identify and train treatment supporters to assist monitoring of TPT adherence and adverse events so as to ensure high TPT completion rates. • Monitor TB and TPT adverse drug reactions and their management. • Strengthen community engagement to increase awareness among general population about TB/TBI, HIV and TPT interventions. • Follow up to monitor individuals who have completed TPT for development of active TB. • Proper recording and reporting for PMTPT.
6.3.4 Role and responsibilities of the CSOs
• Integrate TB contact investigation into their community TB interventions. • Work with the CHWs and other TB networks (e.g., TB survivors) that can contribute to TPT services delivery. • Train and build capacity of community health care workers and other implementers. • Participate in demand creation for TPT among at-risk groups and the community at large. • Ensure community sensitization of TB survivors, PLHIV networks and others on TB, TBI and TPT. • Conduct community TB screening activities and supervising those carried out by community health workers to ensure quality screening and adherence to National algorithms. • Support the roles of community health workers and other key stakeholders (e.g., CTC) in evaluation of eligibility, initiation and completion of TPT. • Resource mobilization to facilitate implementation of TPT activities.
42 6.4 Integrating TPT and other routine services It is important to target everyone at risk of TB as well as those at risk of HIV. Integrated household contact screening for HIV, TB, and non- communicable diseases provides efficient and holistic care to TB, HIV patients and those with TBI. Patients become more welcoming of the CHWs who are known to be offering multiple types of care compared to those who offer only TB/HIV services. This has been shown to help de-stigmatization of the screening visits and maintains confidentiality15. Therefore, CHWs interventions should make TPT services a routine part of HIV/TB/NCD care-bundles.
It is important that the CHW/CBHS and other stakeholders understand
the different treatment modalities for TB and HIV and the increased need to screen for TB and community TB case finding for early identification and initiation of treatment and TPT for those eligible and at risk. All PLHIV should be screened for TB and if found not to have TB should receive TPT. Furthermore, in order to strengthen TB/HIV activities, TB screening and TPT should be integrated in all TB and HIV programs.
6.5 ACSM Support for TB Infection Management
6.5.1 Principles of ACSM
ACSM is an important component of the TB control strategy to ensure long-term, sustained impact. Advocacy seeks to ensure strong commitment to TB control and resource mobilization. Communication aims to favorably change behavior, knowledge, attitudes, and practices among various groups of people. Social mobilization brings together community members and other stakeholders to strengthen community participation for sustainability and self-reliance. The key objective of ACSM is to generate demand for quality TB diagnosis, treatment and increase treatment adherence, leading to cure of all diagnosed TB patients. ACSM helps to improve health communication by bringing about awareness and changes in health perceptions and health seeking behaviors.
Pranay Sinha, Sheela V. Shenoi & Gerald H. Friedland (2020) Opportunities for community health 15
workers to contribute to global efforts to end tuberculosis, Global Public Health, 15:3, 474-484, DOI: 10.1080/17441692.2019.1663361
43 6.5.2 The roles of ACSM strategy on TB Infection The burden of TB among people living with HIV triggered the need for joint efforts in addressing the conditions collaboratively. The TB/HIV collaborative activities have been implemented in Tanzania since 2006; testing for HIV among TB patients and active screening for TB among HIV patients has been scaled-up countrywide. HIV testing among TB patients has increased to 99% in 2017 as compared to 93% in 2015. Furthermore, ART uptake among those TB patients who tested positive for HIV has increased from 85% in 2015 to 99% in 2019. On the other hand, the proportion of TB patients who are co-infected with HIV has decreased from 39% in 2012 to 24% in 2019. To effectively address the challenges of TB/HIV in reference to TPT, different groups are expected to play particular roles; • Policy and decision makers (Parliament, Central Government, Local Government) – promote the use of TPT through their operation organs. • MoH and PORALG – prepare guidelines to promote the use of TPT to community members, empower healthcare workers to administer the uptake of TPT and conduct M&E on the use of TPT in the country. • Implementing partners (IPs) – purchase TPT, support rollout at grassroot and promote its consumption among community members. • Healthcare workers – promote the use of TPT among community members, offer right information about products and expand the coverage of the products in the community. • Community Health Workers (CHWs) – adhere to contact investigation and tracing to TB Infection as stipulated in TB and Leprosy Guidelines as well as promoting the consumption of TPT among community members.
6.5.3 Priority ACSM activities in TPT
• Develop and disseminate TPT IEC materials to respective targeted groups. • Develop and broadcast messages on 3HP in print, electronic and digital media. Including Q & A that will dispel myth about new TPT regimens. • Facilitate key TB experts to appear in health programs of leading National and regional radio and TV stations to create awareness about 3HP. • Train media personnel (producers, presenters, journalists and bloggers) on 3HP
44 CHAPTER 7: PROCUREMENT AND SUPPLY CHAIN MANAGEMENT
This chapter describes the logistics management of TPT medicines which
are among the essential medicines. It describes how the TPT medicines will be quantified, procured, stored, ordered by facilities and distributed. It also explains the roles and responsibilities of the different levels in the logistics system. The Tuberculosis medicines logistic system has three levels which are MSD, district/councils and facility level.
7.1 Procurement, Storage and Distribution.
The medicines for various regimen for TPT will be centrally procured and supplied through the NTLP in the same manner as other TB medicine. The procured TPT regimens would be stored and distributed by MSD as per required standards, procedures and regulations.
Supply of TPT regimen is integrated in the National health commodities
supply chain. All TPT regimens detailed earlier shall be distributed through the National supply chain system by Medical Stores Department (MSD)16. Districts/Councils and high-volume facilities would request TPT regimen from MSD through e-LMIS by using Re-designed logistic system (bimonthly) as per their specific ordering cycle. Combined logistic and morbidity data would be used to determine the needs17.
The facilities (DOT facilities) would submit monthly report through electronic Monthly Report Form (e-FMRF) to the district and order TPT regimens monthly depending on the number of clients. High volume facilities would order TPT regimens bimonthly from Medical Stores Department (MSD).
The DOT facilities maximum stock level will be fixed at 2 months of stock and the minimum stock level will be fixed at 1 month of stock. The maximum and minimum stock levels at the district will be fixed at 4 months and 2 months respectively. At the district, the use of 4 months of supply as the maximum is based on the fact that districts will order TB medicines every 2 months while a minimum of 2 months will provide a district sufficient stock to use while waiting commodities from MSD following placing an order which covers one (1) month stock to cover for the time it takes for orders to be processed and shipped, and one (1) month of buffer stock to cover for events that the need for any supply increases18.
16 Health Commodities Transition Guideline, May 2022 17 Essential Health Commodities Quantification Guideline, July 2018
45 18 Tanzania: Strategic Review of the National Supply Chain for Health Commodities, July 2013
Figure 3: Flow of information, TPT commodities and R & R form
7.2 Reconciliation In the event of loss to follow-up or death or discontinuation of TPT for any reason, the leftover tablets will be communicated in the Report and Request Forms (R & R) prepared by the health facilities. This information on reconciled Medicines will be communicated as per batch number, expiry date and condition of the commodities.
This medicine should at all times be stored in the secured and well- ventilated pharmacy stores to ensure the quality of the medicine is preserved well.
46 7.3 Roles and responsibilities of TB commodity (3HP, 3HR & 6H) managers.
7.3.1 Health care provider:
• Screening of TB suspected clients. • Initiation of TPT to eligible clients. • Ensure rational use of TB medicines by the clients. • Report on ADRs related to medicine. • Ensure quality data are captured and recorded in HMIS tools.
7.3.2 DOT provider:
• Follow up the number of clients on TPT during preparation of the facility monthly report. • Prepare Health Facility`s monthly reports for all Anti-TB medicines including 3HP, 3HR and 6H. • Submit the monthly report form for review and authorization to the facility in-charge and finally sending to DTLC by 5th day of every month. • Ensure the client takes the medicines as recommended based on weight. • Advice the client on the importance of completion of the drug course. • Ensure quality data are captured and recorded. • Routinely perform drug inventory and accountability at the DOT facility. • Ensure commodities are correctly forecasted as per facility needs and ordered timely in accordance with established ordering and reporting procedures. • Ensure rational use of TB medicines at the DOT facility.
7.3.3 DTLC/DACC/DTHO • Receive monthly reports from health facilities, review health facilities report forms for completeness and correctness. • Calculates the quantities of medicines needed by each facility based on the number of clients on each month of treatment as reported by the health facility. • Submit to the District Pharmacist the facility monthly forms with quantities of medicines to issue indicated to facilitate issuing of the needed medicines by the district pharmacist.
47 7.3.4 Facility Pharmacist • Issue TB medicines. • Conduct physical inventory on a monthly basis. • Submit a report on logistics data (stock on hand, adjustments, consumption and number of stocks out days) on a monthly basis. • Ensure quality data are captured and recorded. • Ensure rational use of TB medicines at the health facility. • Advice other health personnel about safety and effective use of medicines. • Routinely perform drug inventory and accountability at the heath facility. • Ensure commodities are correctly forecasted as per facility needs and ordered timely in accordance with established ordering and reporting procedures.
7.3.5 District Pharmacist
• Facilitate and secure redistributions of health commodities within the district or outside the district. • Responsible for compilation, quality checking and approval of all health facilities’ orders and passing them on to zonal MSD in collaboration with the regional pharmacist. • Coordinate recall of unserviceable medicines from health facilities to the district. • Ensure all reports from health facilities are communicated. • Follow up on the safety and proper use of drugs within the district. • Routinely perform supervision and medicine audit to health facilities. • Ensure commodities are correctly forecasted as per facility needs and ordered timely in accordance with established ordering and reporting procedures. • Provide guidance and technical support to health facilities on commodities and technology.
7.3.6 RTLC/RACC/Regional Pharmacist
• Facilitate and secure redistributions of health commodities within the district or outside the region. • Responsible for compilation, quality checking and approval of all districts’ orders and pass them on to zonal MSD. • Ensure all reports from districts are communicated. • Perform supervision and medicine audit. • Coordinate recall of unserviceable medicines from districts to the region.
48 • Follow up on the safety and proper use of drugs within the region. • Coordinate reporting, requisition, distribution and redistribution of commodities. • Provide guidance and technical support to districts on commodities and technology.
7.3.7 MSD • Provide technical support during customs clearance and storage of commodities. • Receive and store medicines properly to ensure that quality is preserved. • Receive, review and process approved orders received from the districts on a bimonthly basis. • Distribute medicines to all districts based on the integrated logistic system (ILS) distribution schedule for each district. • Provide timely and accurate report of stock on hand and distribution status. • Coordinate recall of unserviceable medicines from MSD zones.
7.4 Quantification and quantification assumptions.
7.4.1 Quantification. Annual demand planning for various TPT regimens would be done to contribute to the National level quantification forecasting. The bottom-up quantification approach will be used. Facilities will be required to quantify their requirements based on agreed quantification assumptions of TB medicines and incorporate them in the National demand through their respective regions. National Tuberculosis and Leprosy Program (NTLP) will conduct quantification review biannually and/or when need arise to adjust supply pipeline.
49 50 CHAPTER 8: MONITORING, EVALUATION AND LEARNING
A monitoring, evaluation and learning system is a results-based
management tool to assess progress made toward tracking implementation and achieving TB infection goals. The system generates the information needed for decision-making at different levels of care and management. This chapter aims at guiding HCWs on the following MEL areas: ● Data collection, reporting, data storage ● Data quality assurance ● Data analysis and use ● Supportive Supervision and quality improvement ● Documentation of best practices
8.1 Data collection, reporting and data storage
At the facility level, the individual TBI data for under five children contacts of bacteriologically confirmed TB patients and other at-risk groups will be collected and stored in client identification card and TPT register and then entered into DHIS2 Electronic TB and Leprosy system (DHIS2 ETL). TPT patient treatment card will need to be developed and also DHIS2-ETL will need to be updated to accommodate other at-risk groups.
TPT data for PLHIV on TB screening, TPT initiation, follow-refill and
completion will be captured in patient treatment card (CTC2-card) and then entered in CTC-2 database then exported to CTC3 database and DHIS 2 as aggregate. Health-care workers should be able to accurately fill all relevant data collection tools for TBI services.
8.2 List of data collection tools
● TB01 ● TB03 ● TB18 ● TB10 ● TB17 ● DHIS2-ETL ● CTC 2 cards ● TB screening forms ● Monthly reporting forms ● CTC2 data base ● Logistic Management Information system tools (LMIs) ● TB Presumptive register ● Tracking register ● Community referral forms ● Request and report forms for biological specimen for TB and Leprosy
51 8.3 Analysis and use of data TBI service package include identification of eligible clients, rule out of Tuberculosis, testing of TBI, initiation of TPT and completion of treatment. This information should be captured within the National designated tools for TB and HIV programs; analyzed in cascade fashion to inform programmatic gaps and actions.
8.3.1 Use of data
Data collected are more meaningful when used effectively. The integration of data collection, reporting, analysis, interpretation and presentation helps to improve the quality of the services. Data use differ in all levels of management meaning facility, district, regional and National level. Aggregate or individual level data available at health facility level should be used for: ● Monitoring and identifying patients/clients in need of extra interventions, referrals, care and to alert or remind HCWs on clients/patients with particular needs, thus improve HIV and TB services. ● Administrative purposes to improve access, coverage, quality of services, and efficient use of resources. ● Quantification and ordering of medicines and supplies. ● As basis for planning, developing, and ongoing improvement of TPT Interventions a) At district level, data from facilities will be available and used for: ● Budgeting and allocation of resources. ● Assist the council authorities to plan interventions and monitor activities at the heath facilities ● To make decisions related to construction, expansion of facilities and whether or not to increase human resource at facilities. ● Acquisition and distribution of resources ● Quantification and ordering of medicines and supplies.
b) At regional level, data from districts will be available and used
for: ● Acquiring and distribute resources accordingly. ● To plan for future interventions according to the performance trends. ● To make decisions related to construction, expansion of facilities and whether or not to increase human resource at facilities. ● Budgeting and allocation of resources.
52 ● The data assists the regional authorities in planning interventions and monitor activities at the district levels. ● The region can effectively incorporate district TPT plans into the overall region plans.
c) At the National level data should be used for:
● Monitoring the countrywide trends of TPT ● Commodities quantification ● Policy formulation ● Resources mobilization, acquisition and allocation ● Inform strategic decisions for improvement of interventions of overall council plans.
8.3.2 Data Quality Assurance
Data quality is the degree to which data represent and measure what they are intended to represent and measure when the data collection system was designed. Data Quality Assurance is systematic review of the routine monitoring systems, it involves identification of errors, inconsistencies and other data anomalies, and conducting activities aimed at improving the quality of data and eliminating the errors identified. The facility staff has the following roles in conducting data quality assurance for TBI services: ● Conduct spot checks and cross checks on 10% of records on weekly basis ● Verifying patients’ data between TPT/ART register and DHIS2- ETL, DHIS2 and CTC2 data base for TBHIV data. ● Include issues of data analysis and use in regular facility management meetings ● Convene regular data review meetings to ensure facility data are of high quality
53 Table7: Data quality terms
Accuracy Accuracy refers to the extent to which the data reflect the actual/correct information. It defines validity of the data and is achieved by minimizing errors from recording or interviewer bias and transcription. Completeness Completeness means that an information system from which the results are derived is appropriately inclusive: it represents the complete list of records (eligible persons, facilities, units) and the fields in each record are provided appropriately Confidentiality Confidentiality means that clients are assured that their data will be maintained according to national and/or international standards for data. This means that personal data are not disclosed inappropriately, and that data in hard copy and electronic form are treated with appropriate levels of security (e.g., kept in locked cabinets and/or in password protected files). Completed/used data collection and reporting tools should be stored as per existing national guidelines. Integrity Data have integrity when the system used to generate them is protected from deliberate bias or manipulation for political or personal reasons Precision This means that the data have sufficient detail. For example, an indicator requires the number of individuals who received TB screening and received their screening results, by sex of the individual. In this case, an information system lacks precision if it is not designed to record the sex of the individual who received TB screening. Reliability Data are reliable if they are arguably complete and accurate, measure the intended indicator, are consistent and are not subject to inappropriate alteration over time. Timely Data are timely when they are up-to-date (current), and when the information is available on time. Timeliness is affected by: a) the rate at which the programme’s information system is updated, b) the rate of change of actual programme activities; and, c) when the information is actually used or required.
54 Table 8: NTLP/NACP data assurance activities
Monthly Spot checks Community: CHCW
Provider Facility: DOT provider, ART Nurse, CTC clinician, facility data officer CHMT: DTLC/DACC Cross checks Community: CHCW Provider Facility: DOT provider, ART Nurse, CTC clinician, facility data officer CHMT: DTLC/DACC Desk review Community: Community person in charge HMT CHMT RHMT NATIONAL Site assessment CHMT RHMT Quarterly Supervision checks Facility in charge/DOT provider, ART Nurse, CTC clinician, facility data officer CHMT RHMT NTLP/NACP Ips Desk review RHMT/ NTLP/NACP IPs Site assessment RHMT NTLP/NACP Ips Data review meeting RHMT
8.3.3 Data flow
Recording of patients’ data at the facility is done in TPT registers and patients/client’s cards, then data are entered in DHIS2 ETL. At CTC, the TPT data from ART registers and cards are aggregated into a summary report and sent to the council for entry into CTC2 database according to the National guidelines.
55 Figure 4: Data Flow
It is important that the dimensions of quality data are maintained at each
stage of data recording and compilation. a) Recording: Capturing data on patient management over time and across clinical sites: ● Information is written directly on paper forms or entered into a computer b) Reporting: Routine tracking (monitoring) of priority program management information of summary patient outcome data (evaluation) at health facility, district/council. regional and National levels over a period of time. Health care workers should make sure that cards and registers are updated, complete filled, accurate and reliable.
8.4 Focused supportive supervision
Gaps identified in the cascade analysis of the TBI service delivery, should be used by the National and sub-national levels to prioritize planning and implementation of the support supervision, mentorship and documentation of implementation gaps in the delivery of the TBI services. Despite having focused supervision services, the idea of integrating this supervision with other TB and HIV programmatic areas should be underscored as efficient. Supportive supervision should identify/address barriers to service delivery to improve health services on daily basis.
56 8.5 Documentation of best practice and research questions Documentation of best practices is very important in health care settings. The primary objective in documenting and sharing the best practices is to identify the best ways of doing things and share knowledge with others. This puts everyone on the same page of doing things in the best way to meet the goals. These guidelines encourage HCWs on documenting the best practices and innovations in TBI services especially on coordination, screening, initiation of treatment and treatment completion through the following steps.
Table 9: Best practice documentation
Best practices Gaps/Challenges Lesson learnt Comments identified TBI services coordination
TBI Screening
TBI treatment initiation
TBI treatment completion
Documenting the best practices leads to formulate research questions.
A research question is a question that addresses the gaps/challenges which aimed to be answered by study/research.
8.6 Mobile Health Platforms
Through electronic platforms data entry of clients on TPT should be entered for all those identified as target groups throughout the TPT care cascade. The electronic platforms should facilitate evaluation of TB contacts. It should also allow monitoring of TB contacts throughout the TPT cascade of care and capture data from the stage of TB contact identification, registration, screening for active TB, clinical assessment, TB investigation and treatment. It should be able to prompt the health system when there are gaps in the TPT cascade of care and provide performance indicators. The platform should be able to monitor a patient’s continuum of care when the client develops TB disease after initiation of TPT from the information entered and be able to visualize the data from the dashboard for easy day to day real time monitoring of key PMTPT indicators and performance by the health care workers.
57 Examples of electronic platforms which can be used to monitor PMTPT i. WHO Prevent TB App ii. Tambua TB App iii. DHIS2-ETL iv. Digital Adherence Technology v. Community TB App
58 Annex 1: PAEDIATRIC TB SCORE CHART SCORE IF SIGN OR SYMPTOM PRESENT 0 1 2 3 4 SCORE General features Duration of illness Less than 2-4 weeks More than 4 2 weeks weeks Failure to thrive or weight No weight gain or loss Weight gain weight faltering Weight loss
TB contact None Reported (but Smear positive
no (with documentation) documentation) smear negative Or EPTB
59 TST Negative, Positive not done Malnutrition not improved Present after four weeks of therapy Unexplained fever not responding to Positive appropriate therapy LOCAL FEATURES TB-suggestive features like Chest x-ray infiltration, cavity, or hilar lymph nodes Painless, enlarged lymph Any non- cervical Positive nodes lymph nodes cervical lymph nodes therapy Unexplained fever not responding to Positive appropriate therapy LOCAL FEATURES TB-suggestive features like Chest x-ray infiltration, cavity, or hilar lymph nodes Painless, enlarged lymph Any non- cervical Positive nodes lymph nodes cervical lymph nodes Swelling of bones or Positive joints Unexplained ascites or abdominal mass Positive Central nervous system
60 findings: meningitis*, Positive lethargy, irritability and other behavior changes Annex 2: Dosing charts i. 3HR based regimen recommended dosing chart for the treatment of tuberculosis infection in children Children and Adolescents less than 15 years Strength: 3HR 75mg/50mg Dispersible FDC Strength: 3HR 150mg/75mg FDC Weight Bands 3HR Tablets Weight bands 3HR Tablets 4-7 kgs 1 8-11 kgs 2 25-37 kgs 2 12-15 kgs 3 16-24 kgs 4 38-54 kgs 3 Use Adult
Weight Ranges (Kgs) Dose Given (mgs) Tablets of INH (of 100mg) per Dose
<5 kgs 50 mg ½ tab
5.1 - 9.9 Kg 100 mg 1 tab 10 - 13.9 Kg 150 mg 1 ½ tab (or ½ adult tab) 14 - 19.9 Kg 200 mg 2 tabs 20 - 24.9 Kg 250 mg 2 ½ tabs 30–35 kg 36–45 kg 46–55 kg 56–70 kg >70 kg Isoniazid + Rifapentine (FDC) 300m/300 mg 3 3 3 3 3
iii. INH Dosing Chart
Weight Ranges (Kgs) Dose Given (mgs) Tablets of INH (of 100mg) per Dose
<5 kgs 50 mg ½ tab
5.1 - 9.9 Kg 100 mg 1 tab 10 - 13.9 Kg 150 mg 1 ½ tab (or ½ adult tab) 14 - 19.9 Kg 200 mg 2 tabs 20 - 24.9 Kg 250 mg 2 ½ tabs ≥25 Kg 300 mg 1 adult tablet
62 Annex 3: Core TPT indicators Indicator Indicator definition Data Respo Target Frequency source nsible 2021 2022 2023 2024 2025 Numerator Denominator Core National indicators 1. Percentag Measure TB Number of Number of e of PLHIV screening PLHIV on PLHIV screened for cascade care receiving TB among screened care in the PLHIV for TB in the reporting receiving reporting period care in a reporting period 100% 100% 100% 100% 100% Quarterly DHIS2 NACP 2. Percentag Measure Number of Total number e of TPT TPT eligible of eligible coverage coverage PLHIV PLHIV
63 among among completed/i received care PLHIV eligible nitiated on in the CTC2 PLHIV TPT (3HP, reporting data 3HR, 6H) period ≥95% ≥95% ≥95% ≥95% ≥95% Monthly base NACP 3. Proportion Measure Number of Number of al of PLHIV performanc PLHIV on PLHIV on TPT e of TPT in TPT initiated on developing preventing developed TPT in a active TB in developmen active TB in given a given t of active a given reporting reporting TB among reporting period period PLHIV in a period CTC2 reporting data period <0.1 <0.1 <0.1 <0.1 <0.1 Quarterly base NACP 4. Percentag Measure TB Number of Targets of e of under- screening under-five under-five five performanc household household household e among contacts of contacts of contacts of under-five bacteriologi bacteriologica DHIS2- bacteriologic household cally lly confirmed >90% >90% >90% >90% >90% Quarterly ETL NTLP Indicator Indicator definition Data Respo Target Frequency source nsible 2021 2022 2023 2024 2025 ally contacts of confirmed TB patients to confirmed bacteriologi TB patients be screened TB patients cally screened for TB in a screened for confirmed for TB in reporting TB in a TB patients reporting period reporting period period 5. Percentag Measure Number of Number of e of under- initiation under-five under-five five performanc household household household e of TPT contacts of contacts of contacts of among bacteriologi bacteriologica bacteriologic under-five cally lly confirmed household confirmed TB patients
64 ally confirmed contacts of TB patients eligible for TB patients bacteriologi initiated on TPT in a initiated on cally TPT given confirmed reporting TPT in a TB patients period given reporting DHIS2- period >75% >75% >75% >75% >75% Quarterly ETL NTLP 6. Proportion Measure Number of Number of al of under- performanc U5HHC on U5HHC on five e of TPT in TPT TPT in a household preventing developed given contacts of developmen active TB in reporting bacteriologic t of active a given period ally TB among reporting confirmed U5HHC in a period TB patients reporting DHIS2- on TPT period <0.1 <0.1 <0.1 <0.1 <0.1 Quarterly ETL NTLP Indicator Indicator definition Data Respo Target Frequency source nsible 2021 2022 2023 2024 2025 developed active TB in a given reporting period 7. Percentag Measure the Number of Number of e of under- completion U5HHC U5HHC five status of completed initiated on household TPT among TPT in a TPT in a contacts of U5HHC given given bacteriologic reporting reporting ally period period confirmed
65 TB patients completed TPT in a given reporting DHIS2- period >90% >90% >90% >90% >90% Monthly ETL NTLP 8. Percentag Measure Number of Target e of risk- TPT at risk- number of at- groups (≥5 initiation group risk groups Household among at initiated on for receiving contacts of risk groups TPT TPT in a bacteriologic (≥5 given ally Household reporting confirmed contacts of period TB patients, bacteriologi PWUDs, cally confirmed miners and DHIS2- TB patients, prisoners) >90% >90% >90% >90% >90% Monthly ETL NTLP Indicator Indicator definition Data Respo Target Frequency source nsible 2021 2022 2023 2024 2025 initiated on PWUDs, TPT in a miners and given prisoners) reporting period 9. Percentag Measure Number of Number of at- e of at-risk TPT at-risk risk groups groups (≥5 completion groups (≥5 (≥5 Household among at Household Household contacts of risk groups contacts of contacts of bacteriologic bacteriologi bacteriologica ally cally lly confirmed confirmed confirmed TB patients, TB patients, TB patients, PWUDs,
66 PWUDs, PWUDs, miners and miners and miners and prisoners) prisoners) prisoners) initiated on completed completed TPT in a TPT in a TPT in a given given given reporting reporting reporting period DHIS2- period period >90% >90% >90% >90% >90% Monthly ETL NTLP 10. Proportio Measure Number of Number of at- nal of at-risk TPT at-risk risk groups groups on performanc groups on initiated on TPT e in TPT TPT in a developed preventing developed given active TB in developmen active TB in reporting a given t of active a given period reporting TB among reporting DHIS2- period at-risk groups period <0.1 <0.1 <0.1 <0.1 <0.1 Monthly ETL NTLP 67
