MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS — MODULE A by Alexander Pascual

MODULE MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS

INTRODUCTION

TRAINING FOR HEALTH FACILITY STAFF IN THE PHILIPPINES

MODULE

A Management of Drug-Resistant Tuberculosis Training for Health Facility Staff in the Philippines

Introduction

Acknowledgements National Library of the Philippines Cataloguing in Publication Data Management of Drug-resistant Tuberculosis Training for Health Facility Staff in the Philippines 1) Tuberculosis (Disease) – Multidrug-Resistant Tuberculosis 2) Training Modules ISSN # 2012-2675 Recommended citation: Tropical Disease Foundation and Department of Health, Philippines, 2008. Management of Drug-resistant Tuberculosis Training for Health Facility Staff in the Philippines © Tropical Disease Foundation (TDF) and Department of Health, Philippines (DOH) 2008. All rights reserved. Copying and/or transmitting portions or all of this work without permission, or selling this material or portions of this material for profit, may be a violation of applicable law. The publishers encourage dissemination of these modules and will normally grant permission to reproduce portions of this work. The published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the Tropical Disease Foundation and the Department of Health, Philippines be liable for damages arising from its use. Requests for permission to reproduce, in part or in whole, or to translate the training modules should be addressed to either of the agencies below: Tropical Disease Foundation, Philippine International Center for Tuberculosis, Amorsolo corner Urban Avenue, Makati 1229, Philippines, Fax No. (+63 2) 810 2874; email: tetupasi@tdf.org.ph Center for Infectious and Degenerative Diseases, National Center for Disease Prevention and Control, Department of Health, 3rd Floor, Bldg. 13, San Lazaro Compound, Sta. Cruz, Manila, Philippines, Fax: (632) 711-6804, email: rgvianzon10@yahoo.com

Cover and text design: Digix Design Studio / Alexdesigns.ph Printed in the Philippines

These training modules for Drug-resistant Tuberculosis will be used by the National TB Program, Infectious Disease Office, National Centers for Disease Prevention and Control, Philippine Department of Health and its partners in the Local Government Units in the integration of the Programmatic MDR-TB Management into the National TB Program. The documents were prepared by the core team of the Programmatic Management of Drug-Resistant TB (PMDT) Program of the Tropical Disease Foundation, Philippines with the technical assistance from the WHO: Ma. Imelda D. Quelapio, MD, PMDT Executive Officer & Program Manager Nona Rachel Mira, RN, MPH, Training Officer Virgil Belen, RN, Nurse Clinical Coordinator Ruth Orillaza-Chi, MD, Medical Clinical Coordinator Albert Angelo L. Concepcion, RN, MHSS, Program Coordinator Nerizza Múñez, RPh, Drugs and Supplies Management Coordinator Grace Egos, RMT, MSPH, Laboratory Manager Thelma E. Tupasi, MD, Program Director Jacob H. Creswell, MPH, WHO Consultant With contributions from: Michael Evangelista, RMT – PMDT Laboratory Coordinator John Stuart Pancho, RN – Training Assistant Roberto Belchez, RN - Field Coordinator Gail de las Alas, RSW, MSSW – Social Worker Coordinator The contributions from the following are also acknowledged: The technical inputs, editorial review and coordination provided by Dr. Michael N. Voniatis, WHO Medical Officer for Stop TB in the Philippines; the guidance provided by Ms. Karin Bergstrom of the Stop TB Department, WHO–HQ, Geneva; the technical support of the Stop TB Unit of the WHO Western Pacific Regional Office (WPRO); the collaboration and support of the technical and managerial staff of the National TB Programme, Department of Health, Philippines, in particular Dr. Rosalind G. Vianzon, National TB Program Manager and Dr. Vivian Lofranco, focal point on MDR-TB at DOH; the Center for Health Development, the National Capital Region, the NTP Coordinators of the local government units in Metro Manila, Philippines, the MDR-TB Treatment Center staff, and other partners. The production of the module is supported by WHO Regional Office for the Western Pacific and WHO Headquarters, with funding from Eli Lilly and the United States Agency for International Development. The opinions expressed herein are those of the authors and do not necessarily reflect the views of the World Health Organization and the donors.

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 What is drug-resistant tuberculosis (DR-TB) ?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 TB and MDR-TB as a public health problem. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Global setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Philippine setting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 The DOTS strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 The DOTS expanded framework as applied to PMDT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Health Care Delivery System for MDR-TB Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Purpose of this training course. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Course methods and materials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Learning objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . B: Detect Cases of MDR-TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C: Treat MDR-TB Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D: Inform Patients about MDR-TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E: Ensure Continuation of MDR-TB Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . F: Manage Drugs and Supplies for MDR-TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . G: Monitor MDR-TB Case Detection and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11 12 12 12 12 12 13

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Abbreviations and acronyms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Anti- TB drug abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

INTRODUCTION

Introduction This module provides a general introduction to drug-resistant tuberculosis (DR-TB), the Health Care Delivery System for multidrug-resistant tuberculosis (MDR-TB) Management in the Philippines, an overview of the training modules for the Programmatic Management of DR-TB (PMDT), course methods and materials, learning objectives, a glossary, abbreviations and acronyms in the context of DR-TB.

What is drug-resistant tuberculosis (DR-TB) ? Tuberculosis (TB) and DR-TB, including MDR-TB and extensively drug-resistant TB (XDR-TB), are caused by the same organism, Mycobacterium tuberculosis. In general, TB is considered drug-resistant when the organism is not killed by that anti-TB medicine in a laboratory test called drug susceptibility test (DST). The following are different forms of DR-TB: •

Mono-resistant TB is a form of DR-TB wherein the infecting M. tuberculosis isolate is found to be resistant in-vitro to only one first-line anti-TB drug. Note: The first-line anti-TB drugs include isoniazid (H), rifampicin (R ), pyrazinamide (Z), ethambutol (E), and streptomycin (S)

•

Poly-resistant TB is a form of DR-TB wherein the infecting M. tuberculosis isolate is resistant in-vitro to more than one first-line anti-TB drug, but not to both H and R.

•

Example: H-resistant TB, E-resistant TB, etc.

Example: HE-resistant TB, ES-resistant TB, etc.

Multidrug-resistant TB (MDR-TB) is a specific form of DR-TB wherein the infecting M. tuberculosis isolate is resistant in-vitro to at least the two most effective anti-TB drugs, H and R, with or without resistance to the other anti-TB drugs.

þþ

Example: HR-resistant TB, HRES-resistant TB, etc. A severe form of MDR-TB has been identified and labeled extensively drug-resistant tuberculosis or XDR-TB. XDR-TB is MDR-TB plus resistance to any fluoroquinolone (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin or gatifloxacin) and to any one of the second-line injectable drugs (kanamycin, amikacin or capreomycin).

TB and DR-TB are spread in the same manner. When a person with pulmonary TB (TB affecting the lungs) coughs, sneezes, yawns, speaks, etc., tubercle bacilli are spread into the air in tiny droplets. Other people who breathe in these droplets in significant amount can become infected. The symptoms of TB and DR-TB do not differ with cough of two or more weeks as the main symptom with or without fever, chest and/or back pains, hemoptysis, significant weight loss, and others like sweating, fatigue, body malaise and shortness of breath. However, managing MDR-TB is more difficult than managing TB for the following reasons: • • • •

Detection of MDR-TB requires quality assured culture and DST in addition to microscopy The strategies to manage MDR-TB are more complex and require more resources, logistical, human, and economic, than drug-susceptible TB. Treatment for MDR-TB requires a greater number of medicines that need to be administered for at least 18 months under supervised treatment for 6 days a week The second-line anti-TB drugs that are used are more likely to cause adverse reactions and are less active than the first-line drugs.

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It is hoped that early detection and appropriate treatment of MDR-TB can stop the development of XDR-TB which has proven even more difficult to cure. In the Philippines, the success rate for MDR-TB reached 73% in the 2003 (n=22) and 2004 (n=99) cohorts while for a small number of XDR-TB cases in 1999-2006 (n= 21), it was 48%. In the XDR-TB outbreak in KwaZulu-Natal Province in South Africa 2005-2006, among 53 XDR-TB patients co-infected with HIV/AIDS, mortality was extremely high at 98%. Drug resistance, including MDR-TB and XDR-TB, is caused by a number of factors which include: • • • •

Poor regimen selection Failure to directly observe treatment Irregular drug supply Patient non-adherence to treatment

It is essential to manage MDR-TB in the proper setting to increase the chances of cure, to prevent the spread of resistant TB, and to avoid amplification of resistance

TB and MDR-TB as a public health problem Global setting The World Health Organization (WHO) declared TB a global emergency in 1993 in recognition of the growing importance of TB as a public health problem. About one-third of the world’s population is infected with M. tuberculosis. Worldwide in 2005, there were about 8.8 million new cases of TB disease with 1.6 million deaths. The emergence of resistance to drugs used to treat TB, and particularly MDR-TB has become a significant public health problem in a number of countries and an obstacle to effective global TB control. Multi-drug resistance was found in 63 of 72 countries surveyed in 1994-1999. In many other countries, the extent of drug resistance is unknown and the management of patients with MDR-TB is inadequate. WHO estimates that some 300,000– 600,000 new cases of MDR-TB may emerge every year, with a global preval ence that may be as high as one million cases. Success associated with MDR-TB is generally lower than drug-sensitive TB. In the Philippines, the 2004 success rate for DOTS at the National TB Control Program (NTP) was 85% while that for MDR-TB at the Green Light Committee (GLC)-approved program was 73%. The results of efforts to treat and cure MDR-TB have varied greatly. However, there is evidence to believe that well-managed programs, with a strong DOTS strategy prevents emergence of MDR-TB and can be strengthened to successfully manage MDR-TB and prevent more resistance. In countries where drug resistance has been identified, WHO has recommended that specific measures be taken within TB control programs to address the problem through appropriate management of patients and adoption of effective strategies to prevent the propagation and dissemination of DR-TB, including MDR-TB. Furthermore, addressing MDR-TB is a component of the Stop TB Global Plan 2006-2015 of the WHO Stop TB Partnership.

Philippine setting In 2006, the Philippines ranked 9th globally among 22 countries with the highest TB case notification rate. In the Western Pacific Region, it ranked 3rd. In the Philippines, TB is the 6th leading cause of mortality and morbidity. From the results of the drug resistance survey (DRS) conducted in 2004, 4% among new TB cases and 21% of previously treated cases had MDR-TB. The Tropical Disease Foundation (TDF), in Manila, Philippines adopted the DOTS strategy and self-installed a privatepublic mix DOTS (PPMD) facility within the Makati Medical Center (MMC) in 1999 in collaboration with the NTP of the Department of Health (DOH). In addition to DOTS implementation, the facility initiated activities to address MDRTB by expanding its services through a GLC-approved DOTS-Plus Pilot Project in year 2000. In 2003, the proposal 6 INTRODUCTION

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submitted by the Philippines to the Global Fund which included support for the treatment of 500 MDR-TB patients was approved. In 2004, the public sector was engaged into the existing system of MDR-TB management in the effort to mainstream it to the NTP. Another proposal in 2006 to the Global Fund for the treatment of 2,500 more MDR-TB patients over five years was also approved. This has enabled the stepwise mainstreaming of MDR-TB services into the NTP and the initiation of programmatic DR-TB management in the country. The first points of expansion were Metro Manila and Central Visayas.

The DOTS strategy DOTS is the brand name of the internationally recommended strategy for TB control in response to the global emergency. The DOTS strategy has five key components under the Global Plan to Stop TB 2006-2015: • • • • •

Political commitment with increased and sustained financing Case detection through quality assured bacteriology Standardized treatment with first-line drugs through an effective drug supply management system Supervised treatment with patient support Standardized recording and reporting system for monitoring and evaluation and impact measurement

As part of the Global Plan to Stop TB 2006-2015, the Global MDR-TB and XDR-TB Response Plan 2007-2008 is included as a complementary component of the strategy.

The DOTS expanded framework as applied to PMDT In order to address the additional complex issues of MDR-TB management, the WHO created an expanded DOTS framework organized around the five components of the DOTS strategy wth the same underlying principles as DOTS. However, the expanded framework entails a more complex set of strategies. The expanded DOTS framework includes: • • • • •

Sustained political commitment A rational case-finding strategy including accurate, timely diagnosis through quality assured culture and DST Appropriate treatment strategies that use second-line drugs under proper case management conditions Uninterrupted supply of quality assured first- and second-line anti-TB drugs Standardized recording and reporting system for drug-resistant TB control

Each of the components involves more complex and costly operations than those for controlling drug-susceptible TB. Fortunately, addressing DR-TB usually strengthens national TB control programs. One of the most important components of DOTS that is essential to a successful MDR-TB program is directly observed treatment (DOT), which means that a trained treatment partner or volunteer must observe a patient take each daily dose. DOT or supervised treatment as it will be referred to in these modules is important to: • • •

Ensure that patients take the correct treatment regularly; Notice immediately when a patient misses a dose, find out why, and solve the problem; and Monitor any problem that the patient may encounter with the disease, treatment, or other symptoms.

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Below is a table that shows the similarities and differences between the DOTS strategy and MDR-TB management.

Element

DOTS Strategy

DOTS expanded framework as applied to MDR-TB management

Sustained political commitment

Case finding strategy

quality assured direct smear microscopy (DSSM)

quality assured DSSM, culture and DST

Supervised treatment

Standardized treatment with first-line drugs under supervised treatment, with patient support

Appropriate treatment strategies using first- and second-line drugs under supervised treatment and proper case management conditions with more comprehensive patient support

Uninterrupted supply of drugs

quality assured first-line anti-TB drugs

quality assured first- and second-line anti-TB drugs

Standardized records and reports

4 (designed for DR-TB control)

Health Care Delivery System for MDR-TB Management The DOTS-Plus pilot project in the country has moved to a programmatic approach through PMDT, under a privatepublic mix collaboration. The structure of the health care delivery system for MDR-TB management differs from that for the regular DOTS strategy. In the DOTS structure, the service delivery area needed is a functioning DOTS facility while for MDR-TB management in the Philippines the following types of facilities are required: • •

Treatment Centers Treatment Sites

In general, Treatment Centers are DOTS facilities, public or private, providing comprehensive management for more than 10 MDR-TB patients at one time. Treatment Centers are specialized referral centers which through their link with Culture and DST Centers, are able to detect and confirm MDR-TB cases. Diagnosed patients are registered in Treatment Centers where treatment is initiated with a complete package of services while these patients are sputum-positive. Once sputum-negative and stable, the patients are endorsed to community-based DOTS facilities called Treatment Sites which are nearer patients’ places of residence through a programmatic process of patient decentralization. Treatment Sites, on the other hand, are DOTS facilities, public or private, providing a basic or limited package of services for MDR-TB management for fewer than 10 patients at one time, although the exact number depends on the capacity of each Treatment Site. These facilities provide continuing care to patients endorsed by Treatment Centers until treatment completion. However, even during this time, patients continue to visit Treatment Centers at least monthly and remain to be under their supervision and overall responsibility. While there are differences in the scope of services available at the two service delivery areas for PMDT, there are also common functions such as supervised treatment of all doses which is a must whether at the Treatment Center or at the Treatment Site, health education and counseling, active tracing of interrupters and defaulters, etc.

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The roles and functions of Treatment Centers and Treatment Sites in PMDT are described as follows:

MDR-TB Treatment Centers

MDR-TB Treatment Sites

–– Referral center for MDR-TB suspects

–– Referral of MDR-TB suspects to Treatment Centers

–– Detection of MDR-TB cases (smear microscopy and link to Culture and DST Centers) –– Household contact investigation

–– Identification of MDR-TB suspects (smear microscopy)

–– Registration and initiation of treatment of MDRTB cases –– Residence verification –– Sustainability check –– Supervised treatment especially while sputumpositive

–– Continuing treatment for endorsed cases

–– Bacteriologic follow-up of treatment response through culture

–– Bacteriologic follow-up of treatment response through microscopy

–– Early detection, monitoring and management of adverse drug reactions (ADRs) including serious and uncontrolled ADRs and link to specialists

–– Early detection of ADRs and management of minor ADRs and referral to Treatment Centers for serious and uncontrolled ADRs

–– Active tracing of treatment interrupters and defaulters

–– Programmatic patient decentralization for community-based TB care

–– Acceptance of patients decentralized by Treatment Centers

–– Drug management

–– Drug management (limited to very few patients)

–– Supervised treatment when sputum-negative

–– Supervision and monitoring –– Health and drug education/counselling

–– Health education/counselling

–– Psychosocial services –– Recording and reporting

–– Recording

The first three MDR-TB Treatment Centers in the Philippines are the TDF-MMC DOTS Clinic at the Makati Medical Center (MMC) set up in 1999, the Kabalikat sa Kalusugan (KASAKA)-Quezon Institute (QI) MDR-TB Housing Facility in 2004 and the Lung Center of the Philippines (LCP)- Public Health and Domiciliary Unit (PHDU) DOTS Center in 2005, both in Quezon City. More centers are being set-up as PMDT expands in the country. Likewise, the Treatment Sites are increasing in number as more patients are endorsed from Treatment Centers to these DOTS facilities in the community. These are mostly the public health centers and a number of PPMD units, faith-based organizations and non-governmental organizations. The chart on the next page illustrates how the health care delivery system for MDR-TB management is organized in the Philippines.

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Figure 1. Health Care Delivery System for Programmatic Management of DR-TB in the Philippines National TB Program of the Philippines

Tropical Disease Foundation

National level National TB Reference Laboratory Drug- Susceptibility Testing Centers

Culture Center

Regional level Treatment Center (TC)

Local Gov’t Unit level

Community level

TS TS

Treatment Center (TC)

Microscopy

Treatment Center (TC)

Centers

BHWs/ Volunteers BHWs/ Volunteers

BHWs/ Volunteers

Purpose of this training course In the context of expansion, it is essential to standardize operational procedures, knowledge and skills necessary for PMDT. It is important to train staff routinely involved in the management of MDR-TB as it is being mainstreamed to the NTP. This course is designed to equip health workers with the knowledge, skills and attitudes (KSA) to detect and treat MDR-TB cases, manage first- and second-line drugs, inform patients about MDR-TB, and monitor the success of MDR-TB treatment at both Treatment Centers and Treatment Sites using competency-based training modules. These health workers may include physicians, nurses, midwives, and other health care professionals from the public and private sectors. In order to implement the services for PMDT, Treatment Centers and Treatment Sites will need: –– adequately trained manpower –– adequate supplies of anti-TB drugs, ancillary drugs, and other medical supplies –– supplies for collecting sputum samples (containers, labels) –– access to smear microscopy, culture and DST –– forms and registers for MDR-TB patients 10 INTRODUCTION

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The treatment regimens used to treat MDR-TB, unlike drug-susceptible TB, vary from patient to patient due to factors like DST pattern, and history of previous drug use. It is of utmost importance for health care workers to understand the importance of following the principles of treatment for each specific patient. Otherwise, the patient is likely to receive inadequate drugs, will be prone to treatment failure and may develop XDR-TB. The general principles and practices taught in the course are applicable to drug-susceptible TB as well as all forms of DR-TB. For more detailed information on the detection and treatment of MDR-TB patients, please refer to the other modules of this course, namely Module B: Detect Cases of MDR-TB and Module C: Treat MDR-TB Patients, and to the Guidelines for the Programmatic Management of Drug-resistant Tuberculosis, WHO, 2006.

Course methods and materials

This course uses a variety of methods and instructions, including reading, written exercises, individual feedback, discussions, role plays, demonstrations, and observations in a real health facility. Practice, whether in written exercises or role plays, is considered a critical element of instruction. The complete training course includes the following modules (booklets containing units of instruction). Depending on the structure of your course, you may have been given some or all of these modules: A: B: C: D: E: F: G: H: Ref:

Introduction (includes a glossary with definitions of terms that may be unfamiliar) Detect Cases of MDR-TB Treat MDR-TB Patients Inform Patients about MDR-TB Ensure Continuation of MDR-TB Treatment Manage Drugs and Supplies for MDR-TB Monitor MDR-TB Case Detection and Treatment Field Exercise – Observe MDR-TB Management Reference Booklet on the Management of MDR-TB

The Reference Booklet contains important forms, worksheets, and summaries of procedures taught in the course. It also contains instructions for filling out forms. You can use this booklet as an on-the-job resource. The course is designed for small groups of participants who are led and assisted by “facilitators” as they work through the course modules. The facilitators are not lecturers as in a traditional classroom. Their role is to answer questions, provide individual feedback on exercises, lead discussions, structure role plays, etc. For the most part, participants work at their own pace through the modules, although in some activities, such as role plays and discussions, the small group works together. The modules may be used in several different ways: All of the modules may be completed in sequence without interruption, for example, in a 5-day training session. This will be the format most often used. DOTS facility staff will work through these modules before receiving MDR-TB patients at their facility. • • • • •

One module at a time may be used in a series of short training sessions, for example, one module per week. Selected modules may be used in a training session to teach specific skills. Modules may be used to train staff on the job for specific activities. Motivated health workers may work through modules on their own to teach themselves. Modules may be used as a reference for staff in Treatment Centers, Treatment Sites and DOTS facilities.

INTRODUCTION

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Learning objectives The learning objectives are specified after the introduction in each module. The modules will provide information and examples and allow you to practice certain skills necessary for detecting and managing MDR-TB cases and monitoring progress. Exercises are provided in each module. The skills and information presented in each module are as follows:

B: Detect Cases of MDR-TB • • • • • • • • • •

Identify MDR-TB suspects Refer MDR-TB suspects for screening using theMDR -TB Suspects Referral Form Collect and record patient data from the MDR-TB suspect Fill out and use the MDR-TB Screening Form, the Acknowledgement Form, and the TB Symptomatics Masterlist Make an early referral to the Consilium Provide patient education using the Paunawa or Terms of Understanding Collect sputum samples and request the necessary tests Use laboratory results to identify MDR-TB cases Inform MDR-TB suspects of the results and begin additional care as needed Check household contacts of MDR-TB cases

C: Treat MDR-TB Patients • • • • • • •

Determine appropriate treatment regimen using the DST results and patients’ history of drug use Prepare a patient’s Category IV Treatment Card, including specifying the treatment regimen and dose Administer supervised treatment and record it on the Category IV Treatment Card Recognize side-effects and what to do Determine when an MDR-TB patient is due for follow-up examination Interpret the results of follow-up exams and decide on the appropriate course of action Determine treatment outcome

D: Inform Patients about MDR-TB • • • • • • • • • • • • •

Use good communication skills for informing patients Inform the patient with suspected MDR-TB about the possible diagnosis of MDR-TB and the steps to be taken Communicate messages for the MDR-TB suspect about MDR-TB and the diagnostic process Inform the MDR-TB patient and family about MDR-TB, the procedures to be done for enrollment after Consilium approval, and supervised treatment Communicate messages for the MDR-TB patient and family about MDR-TB, XDR-TB, the procedures to be done for enrollment after Consilium approval, and supervised treatment Provide information about the drugs the patient will take and side-effects they might cause Provide information throughout treatment Provide continuing messages for the MDR-TB patient about the treatment regimen, including the drugs, treatment schedule, side effects, sputum examinations Provide information to the patient to be decentralized Communicate messages for the MDR-TB patient about the decentralization process Communicate messages about HIV and TB, and HIV testing and pregnancy Provide information to the patient at the end of treatment Communicate messages for the MDR-TB patient who has finished treatment and will need to come in for follow up examinations.

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E: Ensure Continuation of MDR-TB Treatment • • • • • • • •

Support MDR-TB patients everyday as they continue to come for supervised treatment Identify patients who may interrupt Category IV treatment and help solve the problem Take necessary actions for an MDR-TB patient who interrupts treatment Trace an MDR-TB patient who interrupts treatment and cannot be located Decentralize MDR-TB patients from Treatment Center to Treatment Site Coordinate medical referrals Coordinate MDR-TB patients’ transfers between MDR-TB treatment facilities Retrieve MDR-TB patients experiencing difficulties while receiving Category IV treatment at Treatment Sites

F: Manage Drugs and Supplies for MDR-TB • • • • • • •

Identify the drugs available for MDR-TB treatment Describe the procurement and forecasting of SLD Trace the distribution of drugs from point of source to point of use Prepare drugs for patients receiving MDR-TB regimens Order using the drug request forms Plan for other supplies Observe good drug management procedures for the safe keeping of anti-TB drugs and supplies

G: Monitor MDR-TB Case Detection and Treatment • • • • • • • • •

Enumerate the group indicators and the specific indicators related to MDR-TB case detection and treatment Define the indicators including their numerators and denominators Refer to the source documents for indicators for case detection and treatment Be familiar with the schedule of reporting for specific indicators Collect data on MDR-TB case detection Collect data on Category IV treatment Calculate indicators Analyze indicators Plan appropriate actions to solve problems

INTRODUCTION

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Glossary The definitions provided here refer to the use of terms in the content of this course and are not necessarily valid in other contexts. It should also be noted that the definitions given here are meant in the context of MDR-TB management, and may vary significantly when used in a drug-susceptible TB context. acid-fast bacilli (AFB) �� bacilli that hold stain color even after washing with acid. Tubercle bacilli are acid-fast bacilli. adherence �� the act of following a rule or procedure as directed. For example, for a TB patient, adherence means taking anti-TB drugs under direct observation by a trained treatment partner. See also compliance. adverse event (AE) �� Any untoward medical occurrence in a patient which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory assessment result), symptom or disease temporally associated with the start of treatment, whether or not it is considered causally related to the drugs or procedures being done in MDR-TB management. adverse drug reaction (ADR) �� an undesirable or unwanted reaction to a drug See also mild ADR, severe ADR anorexia �� loss of appetite bacilli �� rod-shaped bacteria bacillary load �� quantity of bacilli present (may reach over 100 million in a single cavity of the lung). BCG �� Bacille Calmette-Guérin, vaccine against tuberculosis that reduces risk of disease by 50–80% when given before infection. buffer stock �� extra stock kept by the health facility to ensure adequate supplies even if there is increased use or a delay in drug delivery. Category IV regimen �� drug regimen designed to treat MDR-TB patients case of MDR-TB �� a patient in whom multidrug-resistant tuberculosis has been bacteriologically confirmed by drug susceptibility test (resistant to at least isoniazid and rifampicin) and/or as defined by a Consilium. Country Coordinating Mechanism (CCM) �� multi-sectoral country level partnership involving broad representations from government agencies, NGOs, community and faith-based organizations, private sector institutions, individuals living with HIV/TB/ Malaria and bilateral and multilateral agencies that develop and submit grant proposals to the Global Fund, monitor their implementation and coordinate with other donors and domestic programs checking question �� a question asked after giving instruction, intended to check the learner’s understanding, so that more information can be given if needed. chronic case �� a patient who is sputum-positive at the end of a retreatment regimen 14 INTRODUCTION

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cohort �� a group of patients taken collectively by virtue of a common characteristic colony �� growth of M. tuberculosis bacilli in a culture medium. confirmed case of MDR-TB �� a patient with positive culture for M. tuberculosis whose infecting strain is resistant in-vitro to at least isoniazid and rifampicin confirmed through a drug susceptibility test compliance �� the act of following a rule or procedure as directed. For example, for a TB patient, compliance means taking anti-TB drugs under direct observation by a trained treatment partner. See also adherence. comply �� to follow a rule or procedure as directed, for example, to take medicine as directed. Consilium �� a case management team which is a multidisciplinary group composed of progam staff, physicians, nurses and other relevant health care workers with expertise on drug-resistant TB management, which meets regularly to confirm diagnosis and design treatment regimens, assess response to treatment and treatment outcome through a consensus utilizing WHO Guidelines for drug-resistant TB and the National Implementing Guidelines for Programmatic Management of Drugresistant TB (Philippines) contact �� see household contact. continuation phase �� the phase of TB treatment after the intensive phase. The continuation phase for MDR-TB patients starts when the patient has had at least 4 consecutive negative cultures from start of treatment and at least 6 months of injectable use and usually lasts 12 – 18 months, during which the patient stops receiving the injectable. conversion �� changing from sputum smear- and culture-positive to sputum smearand culture-negative. A patient should have two sets of consecutive negative smears and cultures taken 30 days apart. Culture conversion is an early indicator of treatment success. It is the most important objective evidence of improvement. conversion rate �� the proportion of sputum smear- and culture-positive cases that are shown to be sputum smear- and culture–negative cases for two consecutive months of MDR-TB treatment culture �� a method of diagnosis involving growing bacteria in a special medium conducive to their growth. A positive culture is necessary in order to perform a drug susceptibility test. cured (treatment outcome) �� a MDR-TB patient who has completed treatment according to the program protocol and has at least five consecutive negative cultures from samples collected at least 30 days apart in the final 12 months of treatment. If only one positive culture is reported during that time, and there is no concomitant clinical evidence of deterioration, a patient may still be considered cured, provided that this positive culture is followed by a minimum of three consecutive negative cultures taken at least 30 days apart. INTRODUCTION

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decentralization �� the process of endorsing patient care from a Treatment Center to a Treatment Site after fulfilling a set of criteria default �� to interrupt (or interruption of ) TB treatment for 2 consecutive months or more for any reason. defaulted (treatment outcome) �� a patient whose treatment was interrupted for 2 consecutive months or more for any reason. denominator �� in a fraction, the number below the line; the divisor in division. direct sputum smear microscopy (DSSM) �� sputum smear examination done by microscopic examination as the first step to diagnose pulmonary TB and to follow up on a previous smear examination to assess response to treatment. died (treatment outcome) �� a patient who died for any reason during the course of treatment. directly observed treatment �� treatment observed or supervised by a trained treatment partner, either a health care worker or a volunteer. The treatment partner actually watches the TB patient swallow the drugs. See supervised treatment DOTS �� the internationally recommended control strategy for TB. The acronym stands for Directly Observed Therapy – Short-course DOTS-Plus �� a term coined in1998 that refers to the piloting of the management of drug-resistant TB within the context of basic DOTS programs drug-resistance �� the ability of TB bacilli to withstand the effects of anti-TB drugs drug-resistant TB (DR-TB) . �� tuberculosis with bacilli resistant to any anti-TB drug as shown by drug susceptibility testing drug-susceptible TB �� TB with bacilli that are killed by first line anti-TB drugs. drug susceptibility test (DST) �� the final part of the laboratory tests that is done in order to diagnose DR-TB. It is used to know if the strain of TB bacilli that the patient has is resistant to different drugs or not. The diagnosis and treatment regimens for MDR-TB are based on the results of these tests. extrapulmonary TB �� TB affecting organs other than the lungs, for example, lymph nodes, bones, joints, genitourinary tract, meninges, pleura, intestines, etc.. extensively drug-resistant TB (XDR-TB) �� a severe form TB with bacilli resistant to at least isoniazid and rifampicin (MDR) plus resistance to any fluoroquinolone and any one of the secondline injectable drugs (kanamycin, amikacin or capreomycin) failed (treatment outcome) �� a patient is considered to have failed the treatment if two or more of the five cultures during the final 12 months of treatment are positive or if any one of the last three cultures is positive. Additionally, treatment failure can be determined by the clinician who makes the judgment based on poor response to treatment or adverse events. fixed-dose combination (FDC) �� two or more drugs combined in one pill or capsule, in specific dosages, to facilitate correct drug intake. 16 INTRODUCTION

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Green Light Committee (GLC) �� a multi-institutional partnership that promotes access to quality-assured life-saving second-line drugs at reduced cost for MDR-TB treatment, ensures and monitors rational use of second-line drugs, reviews project applications and determines if projects are in compliance with WHO guidelines, and provides technical assistance to ongoing projects. Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) �� an independent organization, governed by an international Board that consists of representatives of donor and recipient governments, non-governmental organizations (NGOs), the private sector (including businesses and philanthropic foundations) affected communities, and multi-lateral agencies whose purpose is to attract and disburse additional resources to prevent and treat AIDS, tuberculosis, and malaria. hemoptysis �� coughing up blood coming from the lungs or respiratory system heredity �� genetic transmission of a quality or trait from parent to child household contact of an MDR TB case �� someone who normally sleeps in the same dwelling unit as the MDR-TB case for at least three consecutive months and has common arrangement for preparation and consumption of food incidence �� the number of new cases of a disease occurring in a defined population during a given time period. indicator �� a measurable number, proportion, percentage, or rate that suggests, or indicates, the extent of a program’s achievement or the level of some condition among the population. intensive phase �� the first phase of MDR-TB treatment, usually lasting at least 6 months, consisting of oral drugs and an injectable. During this phase, sputum and culture conversion usually occurs and clinical symptoms improve. interrupter . �� a patient who has at least one missed dose but less than 2 consecutive months of missed doses in vitro �� describes a condition in a laboratory setting as opposed to one in an actual patient jaundice �� yellowish discoloration of the skin or eyes caused by damage or failure of the liver. mainstreaming �� the act of integrating a process or procedure into the routine or usual setup mild ADR �� an ADR that does not warrant discontinuation of the suspect drug multidrug-resistant tuberculosis (MDR-TB) �� a specific form of DR-TB wherein the infecting isolate is resistant in-vitro to at least the two most effective anti-TB medications, H and R, with or without resistance to other anti-TB drugs

INTRODUCTION

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MDR-TB suspect �� a person who falls into one of the risk groups for MDR-TB, namely • Category I failure • Category II failure • Relapse of Category I and II • Return after default • “Other” type of cases • Non-converter of Category II • Symptomatic contact of an MDR-TB patient • HIV-positive with symptoms of TB meninges �� the membrane that envelope the brain and spinal cord. monitor �� to watch closely or check on a routine basis. mono-resistant TB �� a form of DR-TB wherein the infecting isolate of M. tuberculosis is found to be resistant in-vitro to only one first-line anti-TB drug. mucopurulent �� adjective to describe sputum containing both mucus and pus. Mycobacterium tuberculosis �� tubercle bacillus that causes all forms of tuberculosis, whether drugsusceptible, multidrug-resistant or extensively drug-resistant TB new (type of patient) �� a patient who has never had treatment for TB or who has taken antituberculosis drugs for less than 1 month. non-infectious MDR-TB patient �� an MDR-TB patient undergoing treatment with at least two negative cultures taken one month apart numerator �� in a fraction, the number above the line; the dividend in division. open-ended question �� a question that cannot simply be answered by “yes” or “no” but requires further response. Questions that begin with “why,” “how,” etc. are openended. percentage �� a part of a whole expressed in hundredths. If 50% of a population is female, it means that 50 out of 100 people are female. The following examples show different ways of expressing the same meaning: 50% = 0.50 = 50/100; 4% = 0.04 = 4/100. pleura �� the membrane covering the lung and the wall of the chest cavity containing the lungs. poly-resistant TB �� form of DR-TB wherein the infecting isolate of M. tuberculosis is resistant in-vitro to more than one first-line anti-TB drug, but not to both isoniazid and rifampicin. positive culture �� a) culture that has > 10 colonies of bacilli. b) If a culture has <10 colonies, this must be followed by two consecutive positive cultures. If this is followed by a second culture with <10 colonies, the culture should still be interpreted as positive. Programmatic Management of Drug-Resistant TB (PMDT) �� a case management strategy that addresses drug-resistant TB being implemented by, or in collaboration with national TB Control programs, rather than through individual practitioners’ efforts 18 INTRODUCTION

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prevalence �� the number of all cases of a disease existing in a defined population at a specific point in time or during a given time period. prognosis �� the predicted course that a disease will take; expectations for recovery or decline. proportion �� the relationship of a part to a whole, often written as a decimal fraction or percentage (for example, 0.17 or 17%). pulmonary TB (PTB) �� tuberculosis affecting the lungs. radiographic abnormalities �� abnormalities that appear in X-rays. rate �� a measure of the frequency of some event in a defined population during a given time period, expressed, for example, as 1.5 per 100 000. Rates may also be expressed as decimal fractions (for example, 0.25) or as percentages (for example, 25%). referral �� sending a patient to another health facility or to a clinician. Patients may be referred for diagnosis, initiation of treatment, or special care/ hospitalization for complications, toxicity, etc. regimen �� a plan of treatment specifying which drugs are to be given and the dose, frequency, and duration of treatment with each drug. relapse (type of patient) �� a patient previously treated for TB who has been declared cured or treatment completed, and is again diagnosed with bacteriologically positive (smear or culture) tuberculosis. reserve stock �� see buffer stock resistance �� see drug-resistance return after default (type of patient) �� a patient who returns to anti-TB treatment, bacteriologically positive, following interruption of treatment for 2 consecutive months or more. severe ADR �� an ADR that needs prompt medical intervention and often necessitates discontinuation of the suspect drug serious adverse event (SAE) �� any adverse event which; a) results in death, b)is life-threatening, c) requires in-patient hospitalization or prolongation of existing hospitalization, d) results in persistent or significant disability or incapacity, e) is a congenital anomaly/birth defect, f ) other medically important event which is a medical event that on appropriate medical and scientific judgment, may jeopardize the patient or may require intervention (e.g. medical, surgical) to prevent one of the other outcomes listed in the definition above. Examples of such include, but are not limited to, intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias; or convulsions that do not result in hospitalization; or development of drug dependency or drug abuse. scanty �� result of examination of a sputum smear when fewer than 10 acid-fast bacilli are observed. INTRODUCTION

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side-effect �� a secondary and usually adverse effect of a treatment or drug. smear conversion �� changing from sputum smear-positive to sputum smear-negative. specimen �� sample, a small amount (e.g. urine, sputum) to be tested. sputum �� matter ejected from the lungs through the mouth. sputum smear microscopy �� examination of sputum with a microscope to determine whether acidfast bacilli are present. sputum smear-negative cases �� pulmonary TB patients whose sputum does not contain enough tubercle bacilli to be detectable by microscopy. sputum smear-positive cases �� pulmonary TB patients with at least two sputum specimens containing tubercle bacilli that are detectable by microscopy. stock card �� a card kept with each drug in the storeroom. The stock card is updated whenever drugs are received or dispensed, so that it always shows the actual balance in stock. stock-on-hand �� actual quantity of remaining drug supply from last requisition, which includes the buffer stock, at a facility in a particular time. supervised treatment �� treatment observed or supervised by a trained treatment partner, either a health care worker or a volunteer. The treatment partner actually watches the TB patient swallow the drugs. See directly observed treatment transfer �� as used in this course, changing an MDR-TB patient’s treatment facility to another transfer in (type of patient) �� a patient who has been transferred into another TB reporting unit to continue treatment. transferred out (treatment outcome) �� a patient who has been transferred from another TB recording and reporting unit whose treatment outcome is not known transmission �� the transfer of infection or disease from one person to another treatment after failure (type of patient) �� a patient who is started on an anti-TB treatment after having failed the previous regimen. treatment center �� is a DOTS facility, public or private, providing comprehensive management of more than 10 MDR-TB patients and coordinating with MDR-TB Treatment Sites for the supervision and management of patients endorsed for supervised treatment. treatment completed (MDR TB treatment outcome) �� a patient who has completed anti-TB treatment but does not meet the criteria to be classified as a cure because of lack of bacteriological results (i.e. no evidence of conversion for DOTS patients; fewer than five cultures were preformed in the final twelve months of treatment for MDR-TB patients). 20 INTRODUCTION

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treatment site �� is a DOTS facility, public or private, providing a basic package of MDR-TB management for fewer than 10 patients treatment success �� an indicator calculated by adding the number or proportion of patients cured to those who completed treatment. treatment partner �� a trained health worker or supervised community member who directly observes a TB or MDR-TB patient’s treatment. When it is not convenient for a patient to visit the health facility during regular hours, a community treatment partner may be selected to directly observe a patient’s treatment at a more convenient place and time. tuberculin skin test (TST) �� intradermal injection of 0.1 ml of tuberculin (protein extracted from TB bacilli). The test indicates TB infection but not disease. In an individual infected with TB, a hardening of the skin (or induration) can be observed at the injection site in 48–72 hours. tuberculosis (TB) �� a disease or infection caused by the organism Mycobacterium tuberculosis. Not everyone infected with M. tuberculosis develops symptoms of TB disease, which may include cough, hemoptysis, chest or back pain, fever, weight loss, and tiredness (in pulmonary TB). In this course, TB refers to TB disease rather than infection without disease. tubercle bacilli �� bacilli that cause tuberculosis (Mycobacterium tuberculosis).

INTRODUCTION

Abbreviations and acronyms ADR AFB ART BCG BHW CC CCM CHD CHO DOH DOT DOTS DJNRMH DRS DR-TB DSSM DST EPTB FDC FEFO GFATM GLC HIV LCP LGU MDR-TB MHO MM MMC NTP NTRL PHO PMDT PTB PTSI QI SLD TB TDF TC TS TST WHO XDR-TB

22 INTRODUCTION

adverse drug reaction acid-fast bacilli antiretroviral therapy Bacille Calmette-Guerin Barangay Health Worker culture center Country Coordinating Mechanism Center for Health Development City Health Office Department of Health directly observed therapy brand name for the internationally recommended strategy for TB control Dr. Jose N. Rodriguez Memorial Hospital drug resistance surveillance drug-resistant TB direct sputum smear microscopy drug susceptibility test extrapulmonary TB fixed-dose combination first expiry, first out Global Fund to Fight AIDS, Tuberculosis and Malaria Green Light Committee human immunodeficiency virus Lung Center of the Philippines local government unit multidrug-resistant tuberculosis Municipal Health Office Metro Manila Makati Medical Center National Tuberculosis Program National TB Reference Laboratory Provincial Health Office Programmatic Management of Drug-Resistant TB pulmonary TB Philippine Tuberculosis Society, Inc. Quezon Institute second-line drugs tuberculosis Tropical Disease Foundation treatment center treatment site tuberculin skin test World Health Organization extensively drug-resistant TB

Anti- TB drug abbreviations Am Amx/Clv Cfx Cfz Clr Cm Cs E Eto Gfx H Km

Amikacin Amoxicillin/Clavulanate Ciprofloxacin Clofazimine Clarithromycin Capreomycin Cycloserine Ethambutol Ethionamide Gatifloxacin Isoniazid Kanamycin

Lfx Lzd Mfx Ofx PAS Pto R S Th Trd Vi Z

Levofloxacin Linezolid Moxifloxacin Ofloxacin P-aminosalicylic acid Prothionamide Rifampicin Streptomycin Thioacetazone Terizidone Viomycin Pyrazinamide

References 1. The Stop TB Strategy 2006 – 2015. Geneva, World Health Organization, 2006 (WHO/HTM/TB/2006.368) 2. WHO Report 2007 Global Tuberculosis Control – Surveillance, Planning, Financing. Geneva, World Health Organization, 2007 (WHO/HTM/TB/2007.376) 3. The Global MDR-TB and XDR-TB Response Plan 2007 – 2008. Geneva, World Health Organization, 2007 (WHO/ HTM/TB/2007.387) 4. Tropical Disease Foundation, Inc. (2008). Annual Report to the Green Light Committee. Makati City, Philippines. 5. Quelapio, M. I. D., Egos, G. E., Tupasi, T. E., et. al. XDR-TB in the Philippines. The International Journal of Tuberculosis and Lung Disease, November 2007(11), Supplement 1: S63 6. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs – worldwide 2000 – 2004. Mortality and Morbidity Weekly Report 2006, 55(11), 301 – 305 7. Tupasi, T. E., et al. DOTS – Plus for multidrug-resistant tuberculosis in the Philippines: global assistance urgently needed. Tuberculosis (Edinb) 2003, 83(1-3), 52 – 8. 8. Drug Resistance Surveillance in the Philippines. Manila, Department of Health – National Tuberculosis Program, 2005. 9. Guidelines for the Programmatic Management of Drug-resistant Tuberculosis, World Health Organization, Geneva, Switzerland, 2006. (WHO/HTM/TB/2006.361). 10. Guidelines for the Implementation of the Programmatic Management of Drug-resistant Tuberculosis (PMDT). Administrative Order No. 2008-0018. Department of Health, Manila, Philippines, May 26, 2008.

INTRODUCTION

MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS

TRAINING FOR HEALTH FACILITY STAFF IN THE PHILIPPINES

This course is designed to equip health workers with the knowledge, skills and attitudes (KSA) to detect and treat MDR-TB cases, manage first- and second-line drugs, inform patients about MDR-TB, and monitor the success of MDR-TB treatment at both Treatment Centers and Treatment Sites using competency-based training modules. These health workers may include physicians, nurses, midwives, and other health care professionals from the public and private sectors. This course uses a variety of methods and instructions, including reading, written exercises, discussions, role plays, demonstrations, and observations in a real health facility. Practice, whether in written exercises or role plays, is considered a critical element of instruction. The complete training course includes the following modules (booklets containing units of instruction). Depending on the structure of your course, you may have been given some or all of these modules: A

Introduction (includes a glossary with definitions of terms that may be unfamiliar)

Detect Cases of MDR-TB

Treat MDR-TB Patients

Inform Patients about MDR-TB

Ensure Continuation of MDR-TBTreatment

Manage Drugs and Supplies for MDR-TB

Monitor MDR-TB Case Detection andTreatment

Field Exercise – Observe MDR-TB Management

REF

Reference Booklet on the Management of MDR-TB

ISSN 2012-2675

Department of Health Government of Philippines

Tropical Disease Foundation, Inc. Makati, Metro Manila, Philippines

World Health Organization

Office of the Representative in the Philippines

9 772012 267009 PRINTED IN THE PHILIPPINES

MANAGEMENT OF DRUG-RESISTANT TUBERCULOSIS — MODULE A

Articles inside

Anti- TB drug abbreviations

G: Monitor MDR-TB Case Detection and Treatment

Health Care Delivery System for MDR-TB Management

References