Tuberculosis (TB) is largely under control in the industrialised countries of the ‘Global North’, which means that most of the effort to eliminate TB will fall on the shoulders of those emerging middle-income countries where TB is still an epidemic.
HOW CAN BRICS PROMOTE RESEARCH TO END TB?
In January this year (2013), the health ministers of the BRICS countries (Brazil, Russia, India, China and South Africa) met in New Delhi, and agreed that the five countries will collaborate on research to better control TB.
The BRICS countries have a vested interest in TB research — of the total estimated global burden of TB, 63% of the cases are from BRICS countries.
And, according to Dr Vishwa Mohan Katoch, of the Indian Council of Medical Research, even though the countries all achieved complete (or nearly complete) coverage with the DOTS strategy in the 1990’s, gaps in implementation including barriers in early case detection and effective treatment have resulted in continued chains of transmission and the emergence of multi drug resistance (MDR).
“An unacceptable number of deaths from TB continue to occur in BRICS countries,” he said, speaking at the Stop TB Symposium on October 30, 2013, held just prior to the 44th Union World Conference on Lung Health. “There has been very little change in MDR rates among retreatment cases over a decade, indicating that people are receiving treatment with inappropriate regimens or dosages; or there are interruptions in drug supply problems; poor quality of drugs; or non-adherence.”
Similarly, the fact that the incidence of TB has been declining much slower in the BRICS countries than desired[*] (and not at all in the case of multidrug resistant TB) indicates a huge problem with continued TB transmission.
Dr Katoch thinks that it is essential that the BRICS countries collectively study the transmission dynamics of tuberculosis.
“A combination of methods like spoligotyping and MIRU-VNTR shows good potential for tracing sources of infection. These tools need to be more widely used to study the transmission chains in selected populations — prisons, densely populated areas to study the impact of programmes. While the utility of these methods may be geographically restricted, establishing networks would be helpful,” he said.
The BRICS countries have reached an agreement to collaborate on just this sort of research when their Ministers of Health met in New Delhi on 11 January 2013 at the Second BRICS Health Ministers’ Meeting. While much of the conversation between the health ministers dealt with non-communicable diseases, the communiqué they released at the close of the meeting, also announced their intent to work together on TB research:
The Ministers recognized that multi-drug resistant tuberculosis is a major public health problem for the BRICS countries due to its high prevalence and incidence mostly on the marginalized and vulnerable sections of society. They resolved to collaborate and cooperate for development of capacity and infrastructure to reduce the prevalence and incidence of tuberculosis through innovation for new drugs/vaccines, diagnostics and promotion of consortia of tuberculosis researchers to collaborate on clinical trials of drugs and vaccines, strengthening access to affordable medicines and delivery of quality care.
The Ministers also recognized the need to cooperate for adopting and improving systems for notification of tuberculosis patients, availability of anti-tuberculosis drugs at facilities by improving supplier performance, procurement systems and logistics and management of HIV-associated tuberculosis in the primary health care system.
Dr Katosh highlighted some of the main aims of this collaboration.
- The development of simpler, reliable and affordable diagnostics (especially smear negative/extrapulmonary disease) for case detection, patient management and to monitor transmission
- Promoting innovation for new drugs/vaccines
- Developing consortia/networks for clinical trials of new drugs, diagnostics and vaccines
- Research on access to affordable medicines, vaccines and other health technologies of assured quality
- Developing models for integration of the delivery of quality care for both infectious and non-communicable diseases
- Multicountry trials; consortium approach on therapeutics and vaccines — partnerships among the countries as well as international groups/foundations like AERAS, etcetera
- Innovative public health strategies in post-MDG period including notification
- Implementation research with adequate focus on health systems
Given the rising costs of treatment, especially in the case of MDR-TB, “collaborative research on approaches to reduce the costs of treatment and financing models is expected to be particularly useful”, Dr Katosh said.
Strategy for developing research partnerships in BRICS countries
While the Health Ministers reached an agreement to collaborate on TB research earlier this year, some of the particulars must still be hammered out. Dr Katoch proposed the following:
“Time bound programmes need to be developed on each of the themes identified in Delhi and other declarations. Working groups should be established according to each countries areas of interest, and workshops would be the next step held to help identify specific sub-areas of collaboration with the key participants and stakeholders from BRICS as well as other interested or important agencies and countries.”
The different BRICS countries have different areas of expertise — India for instance has a lot of experience developing low cost pharmaceuticals, while South Africa has developed the capacity to run large multicentre clinical trials — so he believes each country should take responsibility for their own part of the research. “If we put in place such mechanisms in 2013, they could be functional in 2014 very easily,” concluded Dr Katoch.
But if the health ministers in these countries can synchronise their efforts — the solutions that they develop may be more likely to meet the needs of low and middle-income countries.
The importance of evidence for universal health coverage and development goals
None of this is to say that there is no longer any role for development aid to low and middle-income countries. But funding partners should look at how best they can facilitate positive trends in the health sector already underway in the emerging economies, according to Dr Ariel Pablos-Mendez, the Assistant Coordinator and head of Global Health at US Agency for International Development (USAID). One such way is to invest in research that could help resolve some of the challenges to providing universal health coverage for TB.
UNPRECEDENTED GLOBAL ECONOMIC GROWTH, INCREASE IN HEALTH EXPENDITURES LEADING TO IMPROVEMENTS IN GLOBAL HEALTH
The movement towards universal health coverage is not only “feasible, but, I believe, inevitable,” Dr Pablos-Mendez believes told the symposium. “Many countries are experiencing a tremendous economic growth and invest more in the health coverage for their own citizens. “
After centuries or even millennia with little change, over the last few decades, there has been unprecedented global economic growth around the world in terms of per capita income.
“The economies of most of the world have grown dramatically. It has been incredible, it is something that goes far beyond the recent stagnation,” he said. “When I left Mexico 26 years ago, the income per capita was $3000 and today it is $16,000 per capita. It is unprecedented that you have five-fold increases in income per capita in a generation.”
This increase in global wealth has been strongly correlated with growth in the health expenditures per capita. This has been associated with some dramatic results in global health in the last 20 years:
- HIV incidence has been cut by half, TB deaths by 40% and malaria deaths by 30%
- 50% fewer women have died giving birth
- 90 million children’s lives have been spared
- Family planning has empowered women, saved lives and brought a demographic dividend to families and economies
“In the 90’s it was hard to envision something as bold as like the ‘end of maternal & childbirth deaths’, or the ‘elimination of TB’… but now it is possible because of the success we’ve had all around the world,” said Dr Pablos-Mendez. “The improvements in mortality we’ve enjoyed in [the Global North] are now within reach of the rest of the world, in our generation, by 2035.”
There is now enough money in emerging economies to cover an essential package of care providing for the basic health needs of their people.
“This is the most welcome news for our field, not the budget for PEPFAR or the Global Fund, this is the most important news in our space today,” he said.
But there are questions about how to organise the response to best meet these needs. With the growth of income, and the increased spending on health, there is usually been an explosion in the private health sector. This is at least partly because the ministries of health/public health programmes initially don’t have the capacity to respond to the demand.
As a result, a lot of the spending on health is out of pocket, for instance 50-80% of the expenditures in Africa or India are out of pocket. An unfortunate consequence of this out-of-pocket spending, in severe cases, is financial catastrophe and impoverishment. In much of the world, medical bills are the leading cause of impoverishment.
“However, the incidence of financial catastrophe falls to negligible levels when the reliance on direct payment falls to less than 15-20% of total health expenditures,” said Dr Pablos-Mendez. And this provides strong incentive to provide universal health coverage.
According to Dr Pablos-Mendez, many countries have already embraced the concept of universal health coverage, and have adopted strategies to reach that goal with different degrees of success by reforming health care finance, improving the efficiency of the health care system and implementing social protection programs.
Examples include Rwanda, a low-income country, which has achieved universal health coverage, and Ghana, which now has health coverage for about 70% of the population. Recently, Senegal has committed to provide it as well. “It may take years to do, but the idea to provide more public financing of health has generally gained wide acceptance,” said Dr Pablos-Mendez, who added that civil society has a critical role to play in advocating for other countries to provide universal health coverage.
What does that mean for tuberculosis?
TB is a disease of poverty: the poorer the community, the greater the likelihood of being infected with TB and developing clinical disease. TB also fuels poverty: The economic and human impact of TB is many times greater on poor households and upon poor nations than on the developed world. A TB patient can lose several months of work time and earning as a result of TB.
However, it is clear that pooling of resources to provide an expansion in universal health coverage for TB would lead to better outcomes for individuals and society. But with so many TB cases going undiagnosed and untreated, universal health coverage remains out of reach for TB in many countries.
This is particularly true of MDR-TB diagnosis and treatment. Only a small proportion of estimated MDR-TB is diagnosed — and even so diagnosis of MDR-TB is outpacing capacity to treat — in some countries (such as South Africa) diagnosis is far outpacing treatment.
Many of the high burden countries have limited programmatic capacity to address and scale up MDR-TB diagnosis and treatment. Management of MDR-TB is complicated by the limited availability and the expense of second line drugs; and the long duration of treatment (18-24 months) — as well as the high rate of side effects. In addition, there is a lack of paediatric formulations for the second line drugs.
So, among other forms of support, the USAID has made a commitment to promote TB research and innovation in order to optimise, introduce and scale-up existing tools and late stage research or innovations.
About 25% of the research budget is allocated to improving diagnosis, this means validating and increasing the uptake and scale of newly diagnosed tools, such as the Xpert MTB/RIF assay. About 30% goes to new drug development and improving the treatment regimen — in particular, the evaluation of shorter treatment regimens (one example is Standardised Treatment Regimen of Anti-Tuberculosis drugs for patients with multi-drug resistant tuberculosis (STREAM) study, a multicentre study that seeks to build upon the findings of a study conducted in Bangladesh that reported excellent results with a 9 month MDR-TB regimen including gatifloxacin (Van Deun)).
The remaining 45% of USAIDS TB research budget is dedicated to operational research to improve TB case finding and adherence through innovative and country specific approaches.
“This research is critical in order to generate evidence to guide countries on how best to implement strategies that will lead to universal health coverage and address specific technical areas, such as TB,” said Dr Pablos-Mendez. “The current model of development support to these countries needs to be revised. We need to engage lower middle-income countries in new ways: to crowd-back-in local resources and to reorganise domestic financing. Finally, we need to engage the BRICS countries as partners in development, so that BRICS and other middle income countries support TB research and innovation in their own countries to inform the global agenda.”
References:
Katoch VM. How BRICS can promote research to end TB. Stop TB Symposium, 44th Union World Conference on Lung Health, Paris, 2013.
Pablos-Mendez A. Universal Health Coverage: the role of TB and Research. Stop TB Symposium, 44th Union World Conference on Lung Health, Paris, 2013.
Van Deun A, Maug AK, Salim MA et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 Sep 1;182(5):684-92.
[*] With the exception of selected areas of China