TB research and innovation in Latin America

Funding, research and MDR TB in Latin America

Latin America is ideal for large-scale research development in TB. The MDR-TB epidemic has spurred investor interest in research and biotechnology development, which has grown annually from 16.86% in 2005–2006 to 88.03% in 2015–2017 [10].

The region currently attracts TB research and development investors, including large pharmaceutical companies, and Product Development Partners initiatives for the development of TB vaccines, biotechnology in TB and development of new therapeutic alternatives. Latin America accounts for 3% of all cases worldwide [10] and has well-implemented health systems, a critical mass of human resources with proper training, and well-established TB prevention and control programmes.

The most relevant Product Development Partners in Latin America during the past two decades have been: 1) the TB Alliance, focused on developing new drugs and drug regimens to treat drug-susceptible-TB and drug resistant-TB; 2) Aeras and TBVI, which conduct preclinical and clinical trials of TB vaccines; and 3) FIND, which supports a range of diagnostic developers.

Most research and development funding has come from external sources including DFID, USAID, DGIS, NORAD and the Bill and Melinda Gates Foundation, with little support from Latin American governments.

Relationship between national expenditures on TB research and development and incidence of MDR/rifampicin-resistant TB in Latin America

To understand the relationship between TB and MDR-TB rates, and the percentage of national expenditures on research and innovation, we followed the World Bank [5] in examining the Human Development Index, gross domestic product (GDP) per capita, public expenditure on health as a percentage of GDP, and the percentage of GDP devoted to innovation and development activities in Latin America and MDR/rifampicin-resistance TB rates (table 1) [11].

Argentina and Chile had the highest Human Development Indexes (0.83 and 0.847, respectively), while Honduras and Peru had the lowest (0.623 and 0.75, respectively).

The number of patents granted per million inhabitants in 2000–2005 was generally low, with the highest number awarded to residents of Argentina and Cuba [12]. The percentage of GDP devoted to innovation and development activities was <1.0% in all countries except Brazil. Science and technology costs also varied widely, with the largest investments made in Argentina, Brazil and Chile.

The GDP per capita was highest for Uruguay, Chile, Argentina, Mexico and Brazil, but does not correspond to the percentage of GDP devoted to innovation and development activities. With the exception of Uruguay, this was <1.0% in all countries. Brazil devoted 0.90% of GDP to research and development. Health-oriented scientific production per million inhabitants was highest in Chile, Argentina, Uruguay and Brazil and lowest in El Salvador, Honduras and Peru. Based on this analysis, we correlated this data with TB and MDR-TB rates. We consider these rates to be an indicator of the severity of the spread of TB, complexity of the management, and unmet need for TB control. The countries with the highest Human Development Index (Chile, Argentina, Uruguay, in that order) were also the countries with the highest GDP. Uruguay is a special case, because economic growth matched with lowest TB and MDR-TB rates. For Mexico, Peru and Brazil no relationship exists between GDP devoted to research and innovation and low TB and MDR-TB rates. For Brazil and Peru this is understandable given that the increase in the GDP devoted to research and innovation is quite a recent occurrence, specifically as part of a TB reduction strategy.

Stewardship structure and investment in TB research and innovation in Latin America

To articulate a research and development strategy for TB in Latin America, an evolutionary form of research stewardship was formally structured in 1970. An articulated system exists with actors in defined roles and with proper stewardship, governance, management and legal framework. This precondition offers the opportunity to strategically promote TB research and innovation in the region.

However, this network of formal structures for research and innovation in Latin America has so far fallen short in linking research and development with formal domestic policy making bodies. A more efficient integration of formal research and development structures for TB research is necessary.

In table 2, we summarise the formal structure for TB research, the main funders, the amount devoted to TB research and development and the rank for each country [5, 6, 13, 14].

Almost all Latin American countries have formal governance and management structures for TB research (table 2). In Brazil, Cuba, Chile, Peru, Venezuela, Colombia and Argentina [12], both governance and management structures are led by the Ministry of Health, while Argentina, Cuba, Ecuador and Venezuela have mixed structures in which the Ministry of Health and the Ministry of Science and Technology play important roles. In Argentina and Brazil [15], the Ministries of Science And Technology are responsible for management functions [16].

Prioritisation of TB research

The World Health Organization has established four new global TB targets for the 5-year period from 2018 to 2022 [4], these are: 1) to treat 40 million people for TB disease; 2) reach at least 30 million people with TB preventive treatment for a latent TB infection; 3) mobilise at least US$ 13 billion annually for universal access to TB diagnosis, treatment and care by 2022; and 4) mobilise US$ 2 billion annually for TB research [14]. Almost all Latin American countries have policies listing TB research priorities, indicating that a process exists to prioritise, evaluate and adopt TB research. Based on official national TB control programme documents, this priority lists includes the following. 1) Biology and other basic science: to discover fundamental knowledge about latent TB infection, especially in children, Mycobacterium tuberculosis and closely related mycobacterial organisms. 2) MDR-TB diagnostics: to produce better and less toxic TB drugs and to improve preclinical and clinical research on treatments and treatment strategies for TB disease and infection. 3) Vaccines: preclinical and clinical research on TB vaccines, including both preventive and immunotherapeutic vaccines. 4) Operational research including randomised trials, surveillance, and epidemiological and observational studies to evaluate new or existing TB control tools and strategies for vulnerable and key populations.

Discussion and conclusions

• Specific TB research priorities should be defined by the national TB control programmes in Latin American countries themselves and not by external entities. Strategies for defining the lines of TB research in Latin America must include dialogue, participation and interaction of all stakeholders, including the affected communities.

• National TB control programmes must lead the stewardship for TB research and development, with the support of other national science and technology institutions, to establish TB research and development priorities and identify strategies for developing and strengthening TB research and innovation in Latin America to enhance and ensure the academic excellence of the systems.

• While the significance of these systems is widely acknowledged, much remains to be done in order to strengthen local capacity for research and innovation in Latin America.

• In Latin America, visible progress has been made on increasing GDP per capita, but poor correlation with the GDP devoted to TB innovation and research. Closer linkage of TB research and development activities among countries in the region is needed.

• The level of human and technological development is not a limiting factor in establishing a formal structure for the stewardship of TB research. However, it is essential to create conditions for job security and adequate salaries to ensure continuity of work and the appropriate human resource capacity.