There is no doubt that investment and thrust for more effective new diagnostic and treatment tools for tuberculosis (TB) must go up but alongside it is equally imperative to optimally use existing technologies. “Innovation has the ability to change the world. Innovative approaches lead us to concrete outcomes as opposed to knowledge for knowledge sake. We need new ways of doing things. It is trying to solve a problem as opposed to generate new knowledge [by doing research]” said Dr Mel Spigelman, President and CEO of Global Alliance of TB Drug Development (TB Alliance) at the 44th Union World Conference on Lung Health. “We do not optimally use all the resources we have currently.”
Dr Spigelman sees 2014 as a year of accelerated partnerships. For instance, market access is so heavily dependent on effective partnerships we can forge with stakeholders such as the WHO, government agencies such as National TB Programmes (NTPs), NGOs, on the ground implementers, manufacturers, distributors, among others. “Purely commercial model does not work in TB related research and development (R&D) otherwise we will not be here” rightly said Dr Spigelman. In area of R&D, not enough has been done in terms of forging partnerships to bring in new partners and constituencies who have not been involved so far. Enhanced clinical trial capacity and decreased clinical trial costs, enhanced coordination, data and compound sharing and clinical trial planning are other potentially positive outcomes of more effective partnerships.
FINDING MONEY TO DO RESEARCH
Referring to the area of funding Dr Spigelman said that the work that needs to be done actually dwarfs the work that has already been done.
Investment for TB research decreased first time as per the WHO Global Tuberculosis Report 2013 by USD 30 million, said Dr Lucica Ditiu, Executive Secretary of the Stop TB Partnership. She said that the Global Fund to fight AIDS, Tuberculosis and Malaria (The Global Fund) is soon going to request new concept notes for TB-HIV must come at the same time from 38 out of the 41 high burden TB countries. One individual who has HIV and TB co-infection must not be taken care of by two vertical systems.
TB budget has been increased more than three times in India over recent years. But we should be investing not only in R&D but also on finding out what is going wrong at this time by supporting operational research, said Dr Vishwa Mohan Katoch, Director-General of Indian Council of Medical Research (ICMR) and Secretary, Department of Health Research, Ministry of Health and Family Welfare, Government of India.
RESEARCH PARTNERSHIPS IN BRICS NATIONS
Since 63% of global TB burden is in BRICS countries (Brazil, Russia, India, China and South Africa), Dr Katoch advocated to increase research collaborations between these nations. Sharing more about the research partnerships between BRICS nations, Dr Katoch said that meetings are being held to identify specific areas for research collaboration between the countries. BRICS nations might consider doing research projects together and fund their own respective research components. Dr Katoch added that sharing of knowledge generated especially in areas such as epidemiology and intervention research – to study trends, effect of interventions, and role of other factors such as socio-economic aspects.
CALL TO PUSH OPERATIONAL RESEARCH
“TB despite being 100% curable still takes lives. Let us be more proactive. Sometimes we in TB community engage in more waiting than we need to. We wait for new tools and new funding. New tools may change the world. Huge change has happened since WHO declared TB as a global emergency. But three million estimated TB cases were missed as per WHO Global Tuberculosis Report 2013. Can we think about this in a new way? One way is to expand operational research – after all, what use will innovation be of if we fail to employ them in the field properly”, said Jose Luis Castro, Interim Executive Director of the International Union Against Tuberculosis and Lung Disease (The Union).
CHALLENGES FUEL EACH OTHER
“Under-nutrition and growing epidemic from diabetes apart from tobacco use and indoor air pollution are also impacting TB control adversely in South East Asian nations whereas in Sub-Saharan African context, impact of HIV epidemic is more significant on TB. So prevention and treatment policy and programming has to take these factors into account” said Dr Soumya Swaminathan, Director, National Institute for Research in Tuberculosis, Indian Council of Medical Research (ICMR).
“There are huge delays in translating effective interventions into policy at a country level – as there are practical issues of feasibility, acceptability, cost-effectiveness, logistics, among others” said Dr Swaminathan. “Implementation research and effectiveness studies are very important. Screening symptoms were changed when evidence came forth. For example, cough duration as one of the screening signs for TB was reduced from 3 to 2 weeks, and instead of 2 sputum samples now 1 sample is collected.” Another example where innovations showed results comes from Brazil. “In Brazil it has shown that just training of antiretroviral therapy (ART) staff (nursing, counsellors, psychologists, nutritionists among others) led to doubling of TB screening” said Dr Swaminathan.
Involving the programme managers in research and development (R&D) process from the beginning is the key, said Dr Swaminathan. Speaking of other innovations she mentioned the free meals provision for TB patients in Chennai where synergies between existing vertical programmes could make this possible.
Rony Zachariah from Medicins sans Frontieres (MSF) said that “to get research into practice, first get practice into research. If we only invest in upward R&D and not invest in operational research, we will end up with unfinished business.”
SHORTER, CHEAPER TREATMENT FOR MDR-TB ON THE ANVIL
There are positive rays of hope on the anvil in terms of shorter and cheaper treatment regimens for MDR-TB. Innovations are working and we need to generate enough reliable evidence to help change treatment guidance.
Current WHO-approved standard treatment of multidrug-resistant TB (MDR-TB) is of 20 months long duration. But evidence is growing in support of a 9 months long regimen for MDR-TB treatment gives similar treatment outcomes with added benefits of being shorter, cheaper and enhanced treatment outcomes. Dr Arnaud Trebucq of the International Union Against Tuberculosis and Lung Disease (The Union) shared data where 54% of 9153 people who received 20 months WHO-approved standard treatment regimen for MDR-TB got cured compared to 709 people who received the shorter 9 months regimen of whom 88% got cured. The shorter regimen was given in Bangladesh, Cameroon, Benin and Niger. This 9 months regimen costs less too at USD 800 for entire regimen of quality assured drugs.
Dr Arnaud said to Citizen News Service (CNS) that first paper was published in 2010 which showed efficacy of this 9 months regimen for MDR-TB following which it was used in Bangladesh and other countries where too it showed results. “We are implementing this regimen in observation studies in nine countries with support from the WHO and a French aid agency. We have recruited 1000 people with MDR-TB so far. We want to cure patients early and also avoid development of Extensively Drug-Resistant TB (XDR-TB) as due to longer treatment regimens, many more are likely to be lost-to-follow-up thereby increasing the risk of developing further drug resistance.”
This shorter 9 months regimen for MDR-TB is not yet approved by the WHO but with growing evidence, the approval may be considered in future. “WHO approval is an evidence-based process. This is why we are requesting The Union to provide as much evidence as possible [in support of 9 months regimen for MDR-TB]” said Dr Mario Raviglione, Director, Global TB Programme of the WHO.
SOME PROGRESS BUT LONG WAY AHEAD
Ariel Pablos-Mendez from United States Agency for International Development (USAID) said that HIV incidence has been cut by half, TB deaths by 40%, malaria deaths by 30%, 50% fewer women have died giving birth compared to 1990, and 90 million children’s lives have been spared. Family planning has empowered women, saved lives and brought a demographic dividend to families and economies. But there is a long way ahead.
Out of pocket expenditure on health has become one of the leading causes of impoverishments around the world. 80% of health expenditure in India is in private sector. The poorer the community is, the greater the likelihood of being infected with TB and developing active disease.
The economic and human impact of TB is many times greater on poor households and poor nations than on the developed world. A TB patient can lose several months of work time and earning as a result of TB.
While we wait for new technologies to test and treat TB arrive on the ground, we better improvise the way we use existing technologies, approaches and do TB care and control to maximise public health benefits.