references
CHAGAS DISEASE
Health workers at the Mizque health care centre, Cochabamba, Bolivia.
› Chagas disease is endemic in 21 Latin American
countries and in the USA, and is of increasing concern in Europe due to migrant populations. The asymptomatic nature of chronic disease means that it is difficult to know exactly how many people are infected, but current estimates are of 5.7 million people in Latin America alone, indicating that more than 6 million people are likely to be affected worldwide. It is the leading cause of infectious cardiomyopathy in the Western hemisphere. Chagas disease mostly affects those living in poverty, and to date less than 1% of people infected with Trypanosoma cruzi have access to diagnosis and treatment, despite the fact that more than one-half of Chagas disease sufferers live in Latin America’s wealthiest countries – Argentina, Brazil, and Mexico. The only drugs developed which successfully kill T. cruzi parasites are nifurtimox and benznidazole, both more than 40 years old, and although effective, they are used as long treatment regimens and cause frequent side effects. Benznidazole is currently produced in Brazil and Argentina.
results highlighted the importance of early diagnosis and treatment of Chagas patients. Fexinidazole is also being evaluated in adults with chronic indeterminate disease and early stage drug discovery efforts are aiming to identify entirely new chemical entities for development. In response to the lack of access to treatments, DNDi proposed a project to assess the feasibility of scaling up treatment and access to benznidazole, in five countries in the Americas. Previous work undertaken has shown an important paradigm shift over the past two years, from discussing vector control to focusing on the urgent need to scale up access to diagnosis and treatment in Latin America. Throughout 2015, DND i has worked closely with the Colombian Chagas National Control Programme, providing technical support to create the enabling environment needed to scale up access to diagnosis and treatment for Chagas in Colombia. As a result of meetings and discussions between the Ministr y of Health, th e National C o ntr o l P r o gr amm e, an d th e Red Chagas Colombia programme, a comprehensive roadmap for Chagas has been developed which defines operational interventions – such as implementation of pilot projects in four different regions in the country, registration of benznidazole, and support for validation of a new national diagnostic protocol for Chagas disease – which are due to start in 2016. A project in Mexico will focus on short- and medium-term approaches to further assess the disease burden, raise awareness, and ultimately improve patient access by working with the Ministry of Health and other stakeholders. Furthermore, there is the aim to identify and address barriers to access diagnosis and treatment in the USA, as there are large numbers affected by Chagas disease in areas with large populations from endemic countries – such as in California, Florida, and Texas – who are excluded from the healthcare system.
Improving treatments and access to medicines
The benznidazole/fosravuconazole (E1224) trial carried out by DND i and partners confirmed the long-term efficacy of benznidazole, although with the already observed side effects, and further trials are planned to evaluate shorter treatment courses and lower doses of benznidazole with and without fosravuconazole, aiming to maintain or increase efficacy and improve safety. In addition, the recently completed Merck-sponsored STOP Chagas trial in adults with asymptomatic chronic disease confirmed the efficacy of benznidazole and the lack of sustained effect by the azole class of compounds as treatment for Chagas. However, the BENEFIT (Benznidazole Evaluation for Interrupting Trypanosomiasis) trial showed benznidazole treatment was not effective in preventing progression of disease in patients with known Chagas cardiac involvement. These
36 › DNDi Annual Report 2015
