Facing the Reality of Drug-Resistant Tuberculosis in India: Challenges and Potential Solutions: Summary of a Joint Workshop by the Institute of Medicine, the Indian National Science Academy, and the Indian Council of Medical Research (2012)

9

Creating a Blueprint for Action

In the final session of the workshop, moderators and speakers from earlier sessions summarized the major themes that emerged from their sessions and the actions recommended by speakers. This chapter draws on those remarks and on previous chapters in this summary to outline a blueprint for action to guide future decisions, organized by major topics discussed at the workshop. The conclusions and recommendations presented in this chapter were offered by the speakers identified in parentheses in the text and do not represent the consensus of the group or of the conveners of the workshop.

DRUG-RESISTANT TB IN INDIA

India has been conducting an “amazing” expansion of MDR TB treatment with the goal of achieving universal access to treatment, said Salmaan Keshavjee, Harvard Medical School. The country is using primarily an ambulatory model of care delivery with very short hospital stays. Keshavjee emphasized that achieving national goals in India will require strengthening the health care system. Important steps are to build laboratory capacity, recruit and continually train staff, and reorganize the system to deliver care to MDR TB patients.

Initial results from Gujarat discussed at the workshop were “worrisome,” according to Keshavjee. Resistance to the fluoroquinolones was high at 24 percent. High death rates among some patients suggest late case detection, and high default rates suggest problems with the delivery of treatment. On the other hand, Vishwa Mohan Katoch, ICMR, noted that India has in the past had success in tackling major diseases, such as leprosy, despite

its large population and socioeconomic disparities. With regard to leprosy, there was not only success in reducing the numbers of affected people, but also a reduction and near elimination of drug resistance through implementation of a regimented program.

Conclusions and recommendations offered by individual workshop participants regarding drug-resistant TB in India included the following:

• The overall public health care system in India needs to be strengthened to support a strong anti-TB program. (K. Srinath Reddy, Public Health Foundation of India)
• All TB patients should have equitable access to care, and their interests and needs should be protected. (Reddy)
• The basic TB program in India needs to reach out to unnotified and missed cases and to poor and highly vulnerable populations. (Reddy)
• TB medicines should be sold by prescription only and should be prescribed and dispensed by accredited public and private providers. (Reddy)
• A catalog of TB-related activities in India should be undertaken to take stock of the quality and quantity of these activities. Unproductive or ineffective activities should be rejected to make room for innovative new approaches. (Several workshop participants)

PREVENTING TRANSMISSION OF DRUG-RESISTANT TB

As long as people with drug-resistant TB remain untreated or inadequately treated, they have the potential to transmit the disease to others. Infection control in health care facilities and in the community is essential to stop the spread of the epidemic.

Much remains unknown about both the evolution of drug resistance in M.tb. and the transmission of drug-resistant strains among individuals. Certain strains of MDR TB predominate in different countries and regions. An interesting question, said Keshavjee, is whether these strains are more or less fit than other strains in these regions.

Conclusions and recommendations offered by individual workshop participants in the area of preventing transmission of drug-resistant TB included the following:

• Infection control and patient management remain inadequate in many countries. (Keshavjee)
• Treatment should start as early as possible to reduce transmission. (Edward Nardell, Harvard Medical School)

• The potential of surgery to reduce the transmission of TB should be explored. (Rohit Sarin, LRS Institute of Tuberculosis and Respiratory Diseases)
• More research is needed on the fitness and potential for transmission of drug-resistant strains of M.tb. (Sébastien Gagneux, Swiss Tropical and Public Health Institute and University of Basel)

STRENGTHENING LABORATORY CAPACITY

The ability to combat drug-resistant TB is limited by the lack of reliable, quality-assured laboratory tests capable of detecting drug resistance rapidly to support patient management decisions, said Thomas Shinnick, CDC. As Prakash N. Tandon, INSA, observed, a 100 percent sensitive and specific test for TB in general and MDR TB in particular still does not exist, and current tests are cumbersome, costly, and difficult to use widely. Some workshop participants also suggested that although the ideal diagnostic test has yet to be developed, more focused and effective efforts should be undertaken to identify MDR TB using current diagnostics.

India is making good progress in improving laboratory capacity by expanding access to quality-assured conventional and molecular testing, and it is taking advantage of new technologies that are being developed, said Shinnick. But much more work needs to be done to expand the ability of patients to access laboratory services. Rapid tests are promising, but are not yet sufficient to address the problem. The time between ordering a test and implementing a patient management decision based on that test must be minimized. To this end, close communication and coordination among clinicians, TB program managers, laboratory managers, and others will be necessary.

Conclusions and recommendations offered by individual workshop participants with regard to strengthening laboratory capacity included the following:

• In resource-limited settings, standardized treatment regimens rather than individualized regimens may be necessary. (Sarin)
• India needs to strengthen its laboratory capacity with a tiered network at the subdistrict, district, regional, and reference laboratory levels. (Camilla Rodrigues, Hinduja Hospital)
• Validation, quality assurance, and quality control all are essential for DST. (Shinnick)
• Supranational reference laboratories must have the resources and expertise to survey drug resistance and conduct external quality testing for drug susceptibility tests. (Nagamiah Selvakumar, National Institute for Research in Tuberculosis)

• DST laboratories in India need to maintain their proficiency despite shortages of second-line drugs. (Neeraj Raizada, FIND)

ADDRESSING TB AND DRUG-RESISTANT TB
IN VULNERABLE POPULATIONS

Children, people infected with HIV, and migrant and refugee populations all are especially vulnerable to drug-resistant TB and can contribute to its spread. The incidence of drug-resistant TB in these populations remains unknown, especially among children, and this lack of information obscures the extent of the problem. But contact tracing has revealed large numbers of TB and MDR TB cases arising within and from these populations.

Another important vulnerable population, noted Gary Filerman, Atlas Health Foundation, is the prison population. Although the incarcerated and others in congregate settings were not discussed extensively at the workshop, Filerman and Keshavjee noted that the prison populations in almost every country have higher rates of TB and MDR TB than the general population and deserve special attention.

Conclusions and recommendations offered by individual workshop participants in the area of addressing TB and MDR TB in vulnerable populations included the following:

• The burden of drug-resistant TB in vulnerable populations needs to be documented. (Soumya Swaminathan, National Institute for Research in Tuberculosis)
• Better diagnostics are especially important for pediatric populations. (Swaminathan)
• New technologies that can deliver results of DST rapidly for children and people coinfected with HIV are a particular need. (Keshavjee)
• Shorter treatment regimens for MDR TB may be possible in children because of their lower bacillary burden, but clinical trials are needed to test this hypothesis. (Swaminathan)
• New drugs being developed for adult TB patients should be studied in children early in the development process so that pediatric populations can have access to these drugs as quickly as possible. (Swaminathan)
• The possibility of using first- and second-line drugs prophylactically to prevent TB infection in children and other vulnerable populations needs to be studied. (Swaminathan)
• Vulnerable populations and their contacts should be eligible for more aggressive testing. (Mercedes Becerra, Harvard Medical School)

• A global project on pediatric MDR TB could produce much more information about a population that also acts as a sentinel population for infection and treatment issues. (Becerra)¹

COMBATING DRUG-RESISTANT TB THROUGH PUBLIC–PRIVATE
COLLABORATION AND INNOVATIVE APPROACHES

The majority of people in India access private-sector health care services, which means that engaging private health care providers in the fight against MDR TB is essential. In addition, the volume of anti-TB drugs being disseminated by the private sector suggests that many people being treated for TB are not being recorded by public-sector providers. Some second-line drugs are widely available outside the public-sector program. Conclusions and recommendations offered by individual workshop participants on this subject included the following:

• Private-sector laboratories need to be incorporated into the public health laboratory network so they will become an integral part of the national TB control program. (Puneet Dewan, WHO)
• Opportunities to subsidize private laboratories for the early detection of drug-resistant TB should be explored. (Dewan)
• The quality of the case management performed by private providers needs to be improved. (Dewan)
• Private laboratories should be reimbursed, at cost, for drug-susceptibility testing so that these savings can be passed on to patients. (Rodrigues)

Strengthening the Workforce

Human resources to carry out drug-susceptibility testing, MDR TB treatment, and other activities associated with drug-resistant TB are severely limited in India. Coordination of training between the public and private sectors could ease shortages and improve skills. Speakers offered the following conclusions and recommendations on strengthening the workforce:

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¹ Since the workshop, Mercedes Becerra, Assistant Professor, Department of Global Health and Social Medicine, Harvard Medical School, and Soumya Swaminathan, Head, Division of Clinical Research, National Institute for Research in Tuberculosis, collaborated to launch a research network on pediatric drug-resistant TB. As of April 2012, more than 140 individuals from more than 30 countries had come together to collaborate on joint projects through the network, titled The Sentinel Project on Pediatric Drug-Resistant Tuberculosis. More information is available at http://sentinel-project.org/ (accessed April 30, 2012).

• Health workers at all levels need training, retraining, on-the-job training, continuing education, and advanced management training. (Aleyamma Thomas, National Institute for Research in Tuberculosis)
• Training should be followed by in-service monitoring and supervision to detect performance deficiencies, identify new staff in need of training, and identify additional staff needed for current and new interventions. (Thomas)

Using Innovative Technologies

Technology—whether cell phones, electronic medical records, laptops, or biometric identification systems—can facilitate better MDR TB treatment, said Janet Tobias, President, Sierra/Tango Productions, Ikana Media. These technologies can connect health care providers, laboratories, and patients so that treatment can start earlier and be more effective. These technologies also make it possible to offer incentives to private providers and CHWs for identifying MDR TB patients and ensuring that they receive treatment. In addition, technologies make it possible to collect and analyze data that can shape policy decisions and improve patient outcomes. Conclusions and recommendations offered by individual workshop participants regarding the use of technology included the following:

• Pilot programs involving technology should be carried out with health care providers and TB patients to explore ways of expanding treatment. (Tobias)
• Technological interventions in TB care are needed and can go beyond data collection to increase the number of patients identified and improve patient outcomes. (Several workshop participants)
• Economic analyses of the costs of MDR TB and the value of treatment could help make the case to governments for the need to invest in efforts to combat drug-resistant TB. (Tobias)
• Patients should be full partners in drug-resistant TB programs. (Tobias)
• Low-cost, high-impact community-driven models are needed to deliver testing and treatment in difficult-to-reach areas. (Shelly Batra, Operation ASHA)

Creating Partnerships

A recurring sentiment expressed at the workshop was that, given the incidence of MDR TB in India and elsewhere, partnerships are essential to bring the combined resources of multiple organizations to bear on the

problem. Partnerships are needed among various government levels within India, between the public and private sectors, and among international organizations. Finally, patients must become partners with health care providers and governments to win the battle against MDR TB. Conclusions and recommendations offered by individual workshop participants with respect to creating partnerships to combat MDR TB included the following:

• International partnerships and assistance are essential to address MDR TB in resource-limited settings. (Keshavjee)
• INSA should continue to collaborate with other national science academies, including the IOM and National Academy of Sciences, to reduce the threat of drug-resistant TB. (Krishan Lal, INSA)
• Science academies from around the world should convene to develop consensus around actions needed to combat drug-resistant TB. (Tandon)

STRENGTHENING THE SECOND-LINE DRUG SUPPLY CHAIN

Demand for second-line drugs remains too low to sustain multiple suppliers, observed Owen Robinson, Partners In Health. As a result, the prices for these drugs are too high, which is an obstacle to treatment, as are today’s long lead times for the production of drugs. Volume needs to rise to spur competition and lower prices. Financial guarantees or other mechanisms could bring additional suppliers into the market.

Conclusions and recommendations offered by individual workshop participants in the area of strengthening the second-line drug supply chain included the following:

• More manufacturers of quality-assured second-line drugs are needed to lower prices and ensure availability. (Keshavjee)
• Demand for quality second-line drugs needs to be adequately forecast and then aggregated to generate the necessary investments by suppliers. (Robinson)
• Risks need to be aggregated and shared throughout the drug supply chain. (Robinson)
• Prequalification procedures and standards need to be harmonized among countries to reduce barriers to entry into the second-line drug market. (Robinson)
• A working group should be formed to explore challenges to the drug supply chain, ways of overcoming current problems, and possible revolutionary rather than evolutionary changes in the drug supply system. (Robinson)

• Best practices from the retail industry could be adapted to manage the inventory and distribution of second-line drugs. (Prashant Yadav, University of Michigan)
• Drug logistics guidelines are needed for the drug distribution network. (Pradeep Saxena, Government of India)