The facets of TDR research from drug discovery to implementation

First meeting in the Americas region

Fiocruz – TDR partnership reflects fruits of capacity strengthening

Capacity strengthening has been another key feature of TDR’s initiatives in Brazil and the Americas. Among those efforts, the 30-year partnership between Fiocruz and TDR stands as a prime example. The history of collaboration began in 1979 when TDR extended Fiocruz a long-term ‘institution building’ grant. That was followed by more grants in support of specific research or training initiatives, including for basic and applied research in molecular biology, immunology and research on specific diseases, such as Chagas.

The TDR funding to Fiocruz came at a critical time when the institution was in the midst of institutional and financial reorganization, noted former Fiocruz President Dr Carlos Morel in a historical presentation to the JCB. The TDR support for the development of key Fiocruz research departments at a critical moment proved to have a far-reaching impact in terms of leveraging prestige and further resources.

“TDR grants to the molecular and immunology departments were critically important to the rebuilding of Fiocruz in the late 1970s,” Morel observed. “They were critical to getting international support in key areas of science. It was not only a question of money but of prestige, leadership and international recognition.”

Over time, and thanks to many other donors and supporters, the effect has snowballed. Between 2005 and 2007, the institution’s budget has almost tripled, so that by 2007 it stood at US$ 1 billion annually. In comparison, TDR’s support to Fiocruz over the past three decades has totaled a modest US$ 11 million.

Nearly half of the TDR funding has been used to support the training and development of research talent. Here, too, the impact leveraged has been far greater than the monies spent, asserted Professor Rodrigo Corrêa-Oliveira, Vice-Director and Senior Staff Scientist of Fiocruz’s René Rachou Research Centre in Belo Horizonte, in another JCB presentation.

Nearly three-quarters of the immunology experts in Brazil today, for instance, benefited at one point or another from TDR support during their critical career development years, said Corrêa-Oliveira. A former TDR grantee himself, Corrêa-Oliveira credits TDR for his own beginnings in the field. In addition to its support for individual fellowships and training, TDR provided funding, and continues to do so, for the development of training curriculum and manuals used in the region.

The challenge now is to replicate and extend the pattern of success, as exemplified by the Brazil and the Fiocruz story, to other countries in the Americas region, participants at the JCB meeting noted. In a closing address, Dr Paulo Buss, Fiocruz President, cited “the ripple effect of the high-quality research that has been carried out and funded by TDR in Brazil, and its ongoing contribution to the development of other health research projects in this country.”

Dr Zaida Yadon, the Regional Adviser for the Communicable Disease Unit, based at WHO’s Brazil Country Office, called on TDR to extend support for training and research capacity strengthening to Latin American countries that have not yet built capacity such as Brazil’s, in the context of the WHO Global Plan to Combat Neglected Tropical Diseases, 2008-2015.

Control strategies for Chagas disease: the silent killer

An estimated 9 million people in Latin America are affected by Chagas disease, many unknowingly. That is because Chagas is a silent disease that lies dormant for up to 20 years before cardiac and intestinal damage become very evident, eventually leading to pre-mature mortality; on average, people infected with the Trypanosoma cruzi parasite die around the age of 40.

The disease is transmitted when a person unwittingly rubs the contaminated faeces of infected triatomine bugs into wounds, their eyes or mouth. The triatomine bugs become infected by sucking the blood of an already contaminated animal or person. After feeding, they pass the T. cruzi parasite in their faeces.

Control strategies involve vector control, systematic screening to prevent donations of infected blood in endemic countries; detection and treatment of congenital transmission; and treatment of infected children and acute cases TDR has supported basic research and research on new ways of controlling the triatomine bugs that carry the parasite. It also provided funding for the development of diagnostic tools, such as the new recombinant antigen test developed at Fiocruz.

On 17-22 November, a workshop and symposium on the standardization and validation of the clinical use of PCR for T. cruzi DNA detection will be held in Buenos Aries, supported by TDR, INGEBI- Conicet UBA and the United Nations University UNU-BIOLAC. Dr Janis Lazdins-Helds, TDR’s leader of research on drug development for helminths and other neglected diseases, calls the symposium “an extremely important event in Chagas disease research. It is an exercise to validate and standardize the use of available PCR methodologies as tools for evaluating efficacy of new drug candidates in eventual clinical trials.”

While Chagas disease elimination campaigns undertaken in Latin America over the past two decades have halved the number of cases, one of the unknowns still facing the medical community is whether to treat people before symptoms appear, and if this will prevent subsequent complications. Studies so far have been inconclusive. Recently, a TDR steering committee initiated funding that triggered further support for a larger scale clinical trial from the Canadian Institutes of Health Research and the Population Health Research Institute at McMaster University, Canada, as well as the Dante Pazzanese Research Division, São Paulo and research centres in Colombia and Argentina. The so-called BENEFIT clinical trial (Benznidazole Evaluation for Interrupting Trypanosomiasis) will administer benznidazole to 2,000 asymptomatic carriers of Chagas disease and follow them for 5 years.