Revised National Tuberculosis Control Programme DOTS-Plus Guidelines Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi – 110011 Revised National Tuberculosis Control Programme DOTS-Plus Guidelines February 2009 Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi – 110011 Staff members at the Central Tuberculosis Division, Ministry of Health and Family Welfare, New Delhi, the Lala Ram Sarup Institute of Tuberculosis and Allied Diseases, New Delhi, the National Tuberculo sis Institute, Bangalore, the Tuberculo sis Research Centre, Chennai, and the World Health Organization, New Delhi, contributed to the development of the RNTCP DOTSPlus guidelines Table of contents Page Introduction…………………………………………………………………………….. 1 1. Background…………………………………………………………………….. .2 2. Framework for effective control of multidrug-resistant TB………………….8 3. Government commitment and coordination……….…………..……………..10 4. Case finding and definitions…………………………………………………...15 5. Diagnosis and evaluations…………………………………………………..….20 6. Laboratory aspects……………………………………………………………..25 7. Treatment of multidrug-resistant TB.…………….…………………………..39 8. MDR-TB in special situations………………….………………….……….… 46 8. Monitoring and management of adverse drug reactions……………………54 10. Treatment delivery and adherence…………………………………………...60 11. Human resource development for DOTS-Plus under RNTCP……………..66 12. Logistics of second-line anti-TB drugs…….…………………………………70 13. Recording and reporting system ……………………………………………..74 Annexures I. RNTCP Request for culture and drug sensitivity testing II. History of anti-tubercular drugs III. Referral for DST Register (held at the DTC) IV. IRL Culture and DST RegisterV. DOTS-Plus Referral for treatment form VI. Follow-up schedule during Category IV treatment VII. Checklist for initial evaluation and treatment surveillance VIII. RNTCP DOTS-Plus treatment card IX.RNTCPDOTS-PlusTreatmentRegisterX. RNTCP CAT IV TB Identity Card XI. RNTCP Quarterly report on Category IV case finding XII. RNTCP DOTS-Plus six month interim report XIII. RNTCP DOTS-Plus 12 months culture conversion report XIV. RNTCP Quarterly report on the result of treatment of MDR-TB patients on Category IV treatment regimens registered 31-33 months earlierXV. Evaluation at completion of Category IV treatment XVI. Quarterly report on Cat IV drug logistics XVII. Roles of the various facilities under RNTCP DOTS-Plus XVIII. Job responsibilities of various categories of staff under DOTS-Plus XIX. Second Line anti-TB drugs information sheets Abbreviations and Acronyms AFB Acid Fast Bacilli CPContinuationPhase CPCCetyl PyridiniumChloride CNS Central Nervous System CsCycloserine CTD Central TB Division DMC Designated Microscopy Centre DOT Directly Observed Treatment DRSDrugResistance Surveillan ce DSTDrugSensitivityTesting DTC District TB Centre DTO District TB OfficerEEthambutol EQA External Quality Assessment Eto Ethionamide GFATM Global Fund to fight AIDS, TB and Malaria GLC Green Light Committee GoI Government of India GMSD Government Medical Store Depot H Isoniazid HAART Highly Active Anti-Retroviral Therapy HCW Health Care WorkerHIV Human Immunodeficiency Virus HRD Human Resource Development IP Intensive Phase IRLIntermediateReference Laborator y Km Kanamycin LJ Lowenstein -Jensen LRS Lala Ram Sarup TB Institute, Delhi LTLaboratoryTechnician MDR-TB Multidrug-resistant Tuberculo sis MICMinimal Inhibitor y Concentration MO Medical OfficerMO-PHI Medica l Officer – Peripheral Health Institute MO-TC Medical Officer – TB Control NaClSodiumChloride NGO Non-Governmental Organisation NRLNationalReference Laborator y NTI National TB Institute, Bangalore PASp-aminosalicylicacid NTM Non-tuberculous Mycobacteria Ofx Ofloxacin PNBp-nitroben zoic acid RRifampicin RNTCPRevisedNationalTB ControlProgramme S Streptomycin SEARO WHO South-East Asia Regional Office SNRL Supra-National Reference Laboratory SOP Standard Operating Procedures STDC State TB Training and Demonstratio n Centre STLS Senior TB laboratory SupervisorSTO State TB OfficerSTRStandardizedTreatmentRegimen STS Senior TB Treatment SupervisorTB Tuberculosis TRC TB Research Centre, Chennai VCTC Voluntary Counselling and Testing Centre WHO World Health Organization Z Pyrazinami de ZNZiehl-Neelsen 1 INTRODUCTION The emergence of resistance to drugs used to treat tuberculo sis (TB), and particularly multidru g-resistant TB (MDR-TB) , has become a significant public health problem in a number of countrie s and an obstacle to effective TB control. In India, the available information from the several drug resistance surveillance studies conducted in the past suggest that the rate of MDR-TB is relatively low in India, this translates into a large absolute number of cases and as yet the management of patients with MDR-TB is inadequa te. Specific measures are being taken within the Revised National Tuberculosis Control Programme (RNTCP) to address the MDR-TB problem through appropr iate management of patients and strategies to prevent the propagat ion and dissemination of MDR-TB. Traditionally, DOTS-Plus refers to DOTS programmes that add components for MDR-TB diagnosis, managemen t and treatment. These guidelines promote full integration of DOTS and DOTS-Plu s activities under the RNTCP, so that patients with MDR-TB are both correctly identified and properly managed under the recommendations set out in this document. Finally,theguideline introducesnewstandardsforregistering,monitoringandreportingoutcomesofmultidrug -resistantTB cases.Thisuniforminformationmanagementsystemwill allowsystematic,consistent data collection and analysis which will facilitate appropr iate supervision and monitoring of the DOTS Plus activities and will play an important role in shaping future policies and recommendation s. 2 CHAPTER 1: BACKGROUND 1.1 Chapter objectives The chapter summarizes key information on the emergence of drug-res istant TB, its public health impact, experience gained in patient management, and strategies for addressing drug resistance within RNTCP. 1.2 Recent developments 1.2.1 Prevention of MDR-TB It is well known that resistance levels are higher in areas with a poorly performing DOTS programmes. Use ofinadequate regimens and inapprop riate directly observed treatment (DOT) leads to increase in drug resistance levels in the community. It has been acknowledged that good treatment is a pre-requisite to the prevention ofemergence of resistance. RNTCP recognises that implementation of a good quality DOTS programme is the first priority for TB control in the country. Prevention of emergence of MDR-TB in the community is more imperative rather than its treatment. Provision of DOTS-Plus for management of MDR-TB, is a supplementary service under the expanded framework of the DOTS package. Therefore in every DOTS implementing unit ofthe country, DOTS would be prioritised above DOTS-Plus with the view that DOTS reduces the emergence ofMDR-TB, and therefore the need for DOTS Plus over time. 1.2.2 Expansion of the DOTS package Over the past few years, the basic package of DOTS for TB control has been expanded in many areas to includecomponentsthataddressadditionalchallenges suchas TB/HIVco-infection,multidrug-r esistantTB, contributin gto healthsystemstrengthening,engagingall careproviders,empoweringpatientsand commun ities,and enablingandpromotingresearch.Emphasisonexpandinglaboratorycapacity (smearmicroscop y first, then culture/dru g sensitivity testing) and the use of quality assured drugs, are important parts of this more comprehensive approach to TB control. 1.2.3 Introduction of DOTS-Plus The first WHO endorsed DOTS-Plus programmes began in 2000. At that time, the Green Light Committee (GLC) was established to promote access to high quality second-line drugs for appropriate use in TB control programmes.DOTS-Pluspilotprojects havedemonstratedthefeasibility andeffectivenessofMDR-TB treatment in less affluent countries. In 2002, the Global Fund to fight AIDS, TB, and Malaria (GFATM) started financing TB control programmes , including MDR-TB, thus greatly reducing the economic barrier to MDR3 TB control. Since then, DOTS-Plus projec ts have multiplied rapidly. By the end of 2007, 67 projects in 52 countries approved by the GLC, with a cumulative total of over 30,000 MDR-TB patients, had been launched worldwide, many of them with financial support from the GFATM. Based on data and experience from these projects,practicesandfurther scientificevidencehave emergedregardingservicesforMDR-TB.DOTS-Plus programmes can and should strengthen the basic DOTS strategy. 1.2.4 Integration of TB services Detection and treatment of all forms of TB, including multidrug-resistant forms, should be integrated into national TB control programmes. Improperly treated patients with resistant strains of TB are a source ofongoing transmis sion of resistant strains, resulting in added future costs. The framework for DOTS-Plus treatment of MDR-TB cases presented in this document is to be integrated into the RNTCP DOTS strategy. 1.3 Causes of drug-resistant tuberculosis Drug-resis tant TB has microbial, clinical, and programmatic causes. From a microbiolog ical perspective, the resistance is caused by a genetic mutation that makes a drug ineffective against the mutant bacilli. An inadequateorpoorlyadministeredtreatmentregimen allowsdrug-resistantmutantsto becomethedominant strain in a patient infected with TB. Table 1.1 summarizes the common causes of inadequate treatment. However it should be stressed that MDR-TB is a man-made phenomenon – poor treatment, poor drugs and poor adherence lead to the development of MDR-TB. Table 1.1 Causes of inadequate treatment 1 Providers/Programmes: Inadequate regimens Drugs: Inadequate supply/quality Patients: Inadequate drug intake -Absence of guidelines or
