by Alonso-Padilla J, Abril M, Alarcón de Noya B, Almeida IC, Angheben A, Araujo Jorge T, Chatelain E, Esteva M, Gascón J, Grijalva MJ, Guhl F, Hasslocher-Moreno AM, López MC, Luquetti A, Noya O, Pinazo MJ, Ramsey JM, Ribeiro I, Ruiz AM, Schijman AG, Sosa-Estani S, Thomas MC, Torrico F, Zrein M, Picado A. PLOS Neglected Tropical Diseases 2020, 14(4): e0008035. doi: 10.1371/journal.pntd.0008035

Summary: Only a small fraction of patients with Chagas disease are properly diagnosed and treated. Currently, there is no test for the early assessment of treatment efficacy. Development of a test to determine in a timely manner whether a patient with Chagas disease has successfully responded to treatment has been identified as a priority. The authors present a target product profile (TPP) specifically describing the technical and performance characteristics required. Two use scenarios are considered: day-to-day healthcare provision, and clinical evaluation of new anti-Tcruzi drugs or alternative regimens of currently available drugs. The TPP described in this article can guide the development and uptake of these tests, which will be fundamental both to managing patients and evaluating new drugs or regimens.

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by Mussa Abujamra Aith F, Forsyth C, Aparecida Shikanai-Yasuda M. Tropical Medicine Infectious Diseases 2020, 5(2): 62. doi: 10.3390/tropicalmed5020062

Summary: This study discusses the legal framework surrounding access to healthcare for Bolivian migrants with Chagas disease living in São Paulo, Brazil. Although the right to healthcare is constitutionally guaranteed for all, in practice, immigrants, especially those without documentation, encounter barriers to initiating treatment for Chagas disease. Access to healthcare for Bolivian migrants could be improved by providing them with the primary health care system (SUS) card; this would also provide a potential pathway toward regularization of status. The approval of clinical protocols and therapeutic guidelines for Chagas disease is an opportunity to improve care for all Brazilians with Chagas disease. Programmes with multidisciplinary teams should be developed, taking into account the specific social and cultural needs of the migrant Bolivian population.

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by Molina-Morant D, Fernández ML, Bosch-Nicolau P, Sulleiro E, Bangher M, Salvador F, Sanchez-Montalva A, Ribeiro ALP, de Paula AMB, Eloi S, Correa-Oliveira R, Villar JC, Sosa-Estani S, Molina I. Trials 2020, 21:328. doi: 10.1186/s13063-020-4226-2

Summary: Despite modest cure rates in adult chronic patients and its safety profile, benznidazole is the drug of choice to treat Chagas disease. Both the currently recommended dose and duration of treatment are under discussion and may be optimized. The authors describe a study protocol for a phase II, randomized, non-inferiority, double-blind, multicentre international clinical trial, MULTIBENZ, to assess different dose schemes of benznidazole compared with the standard treatment regimen for the treatment of Chagas disease in the chronic phase. MULTIBENZ may help to clarify which is the most adequate benznidazole regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood.

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First “World Chagas Day” highlights how vulnerable many patients are

Doctors in the United States that treat people with Chagas disease, a parasitic illness transmitted by the “kissing bug” in the Americas, are increasingly worried about the estimated 30,000 to 45,000 people that are at increased risk of complications from COVID-19 because they have Chagas-related heart problems.

Only 0.3% of the 300,000 people living with Chagas disease in the United States have accessed treatment, and many of them are from the socially vulnerable populations that are especially hard-hit by the COVID-19 crisis in the United States. Chagas can cause life-threatening heart damage and/or gastrointestinal complications if not treated early.

We are very concerned about our patients – while Chagas is transmitted within the US by native kissing bugs, most of our patients were born in Latin America and today face multiple barriers to accessing healthcare,’ said Dr Rachel Marcus, MD, FACC, Medical Director, LASOCHA (Latin American Society of Chagas). ‘While Chagas-related cardiomyopathy (a disease of the heart muscle) is a potential risk factor for a severe form of COVID-19, we are also worried that many of these people live under the federal poverty line, may not have paid time off, and are forced to continue to put themselves at risk during this crisis – or suffer severe economic deprivation.’

More research is needed on the interaction between Chagas disease and COVID-19. However, people with heart conditions have been more susceptible to COVID-19, and up to 30% of people with Chagas disease suffer from cardiac complications.

Today is the first-ever World Chagas Day – a critical opportunity to raise awareness about this deeply-neglected disease, which affects 6-7 million people, primarily the poor, vulnerable, and marginalized – in Latin America. Most people in the US with Chagas disease do not realize they have the infection, and many healthcare providers are not familiar with the disease, which can remain asymptomatic for decades

It is absolutely essential – particularly now – that health-care providers in the US learn more about Chagas disease, so they can identify patients potentially at high-risk during this pandemic,‘ said Dr Sheba Meymandi, Director of the Center of Excellence for Chagas Disease (CECD) at Olive View-UCLA Medical Center. ‘Although we have an effective treatment for Chagas disease, there is an urgent need to increase access to testing for both Chagas disease and COVID-19.

Fear, stigma, gaps in the health system, and lack of awareness in the medical community are among the barriers keeping the most vulnerable from accessing essential care for Chagas disease, a leading cause of heart disease in the Americas, according to a paper published earlier in the year by the CECD, the not-for-profit drug development organization Drugs for Neglected Diseases initiative (DNDi), the CECD, and the international medical humanitarian organization Doctors Without Borders/Médecins Sans Frontières (MSF). All of these barriers are compounded by the COVID-19 pandemic.

For more information on the first-ever World Chagas Day, please visit the websites below:

Media contact

DNDi North America
Ilan Moss
Tel: +1 646 266 5216
imoss@dndi.org

Photo credit: Angela Boatwright/DNDi

Starting this year, April 14th will serve to give visibility in the global health agenda to the challenges faced by people affected by Chagas disease, most of whom live in low-income contexts and highly vulnerable health conditions.

For the first time in the 111 years since the first case of Chagas disease was diagnosed in humans, we are celebrating World Chagas Day, which was established by the World Health Organization (WHO) on April 14th to remind us of the challenges faced by those affected by this neglected disease.

Well aware that the COVID-19 pandemic requires maximum attention at this critical moment, the aim of marking this first-ever World Chagas Day is to remember the people affected by this disease, which has historically been given low priority in health agendas. This is all the more important at a time when many of those suffering from Chagas disease are amongst the population groups vulnerable to the COVID-19 pandemic.

Chagas disease is caused by the parasite Trypanosoma cruzi, which is mostly transmitted through the feces of the triatomine bug. This bug is commonly known under several names such as “vinchucas”, “chinches”, or “pitos”, and  it is found in the southern United States and all over Latin America. Other common transmission routes are from mother to child during pregnancy, oral, through blood transfusions, and organ transplants. The different transmission routes, together with migratory flows over the last few decades, have made the disease a global challenge.

Approximately 30% of those who become infected with Chagas disease develop serious complications that mainly affect the heart and also lead to neurological and gastrointestinal disorders at a lesser level.

It is estimated that at least 7 million people are infected worldwide. Every year, close to 9,000 children are born with the parasite Trypanosoma cruzi, which causes the death of more than 12,000 people each year. It is also estimated that more than 75 million people worldwide are at risk of becoming infected. As a result, diagnosis and early treatment are crucial, with current treatments achieving very good results.

The International Federation of Associations of People Affected by Chagas disease (FINDECHAGAS) is calling for health authorities in countries where cases have been detected ‘to maintain prevention programmes so that to ensure that as many people as possible are protected’. They also highlight the need to ‘give priority to attention and treatment to people with a positive result, given that, in many cases, this will make a difference between staying healthy or falling ill, or between life and death’.

World Chagas Day was established last year during the World Health Assembly to respond to a request presented by FINDECHAGAS to reverse more than a hundred years of silence and lack of visibility around Chagas disease.

The current COVID-19 pandemic is challenging commitments and support to health systems and universal health coverage leaving nobody behind. To end Chagas disease as a public health issue, efforts must be intensified to control all the transmission routes, strengthen and improve current diagnostics and treatments, develop new tools, and extend comprehensive health coverage to all people living with the disease or at risk of getting infected. At the same time, efforts must be made to promote communication and develop disease awareness.

To these ends, it is vital that over the next decade, policymakers and funders work more closely and willingly with the community of people affected by Chagas disease, researchers, organizations, and health professionals fighting to overcome the challenges posed by Chagas disease.

As FINDECHAGAS reminds, ‘it is of utmost importance that people living with Chagas disease receive the information needed for adequate prevention and the appropriate attention when necessary, even more during the COVID-19 pandemic. For a long time, we have stayed hidden behind statistics and numbers. But we are human beings, and now is the time to make ourselves visible as such before health authorities worldwide.’

As of April 14, FINDECHAGAS, together with the WHO/PAHO and other organizations part of the Global Chagas Coalition, as well as other health institutions and alliances, will be publishing content on Chagas disease and affected people through their networks to raise awareness.

Current data and estimates

More than 7 million people affected

30,000 new cases per year

More than 12,000 deaths per year

More than 75 million people are at risk of becoming infected either by vector, or congenitally, orally, through blood transfusion, and organ transplant

The disease is endemic in 21 countries in the Americas, with Argentina, Bolivia, Brazil, Colombia, and Mexico being the countries with the largest number of affected people

In non-endemic areas, the disease is present on all continents, with the largest number of people affected in the United States and Spain.

Reference pages

Photo credit: Felipe Abondano-DNDi

by Echeverría LE, Marcus R, Novick G, Sosa-Estani S, Ralston K, Zaidel EJ, Forsyth C, Ribeiro ALP, Mendoza I, Falconi ML, Mitelman J, Morillo CA, Pereiro AC, Pinazo MJ, Salvatella R, Martinez F, Perel P, Liprandi ÁS, Piñeiro DJ, Molina GR. Global Heart 2020, 15(1): 26. doi: 10.1016/j.bbadis.2019.165628

Summary: The WHF IASC Roadmap on Chagas disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. The authors propose strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.

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DNDi aims to deliver new, safer, more affordable and effective treatments for people affected by Chagas disease. DNDi is also focused on improving access to diagnosis and treatment using existing tools.

DNDi’s current Chagas disease portfolio includes:

R&D discovery stage iconDiscovery

  • Screening: To identify new hit series that could be progressed and become new drug candidates for Chagas disease, DNDi tests chemical compounds for activity against Trypanosoma cruzi. High-throughput screening of compounds from natural product and synthetic compound collections from partners or commercial suppliers have been conducted, and hits have been identified and are currently being progressed.
  • Chagas hit-to-lead: DNDi has continued its efforts in screening chemically diverse libraries to replenish the discovery pipeline. Confirmed new hits are continuously feeding the hit-to-lead pipeline. In 2019, a new consortium was established in collaboration with University of Campinas and University of Sao Paulo in Brazil. Through a team of scientists working in a global network, PITE (Research Partnership for Technological Innovation) aims to deliver a high-quality pre-clinical candidate compound that could become a new treatment for Chagas disease.
  • NTD Drug Discovery Booster hit-to-lead: Screening activities were placed on temporary hold in early 2019 to focus efforts on transitioning existing hit series into lead optimization projects. Two hit series are currently under further investigation with Takeda, and work is underway to transition additional series for potential lead optimization in 2020.
  • Daiichi-Sankyo Chagas hit-to-lead: The frontrunning series that is the current focus of this hit-to-lead project has clear activity against the T. cruzi parasite and will be progressed for Chagas disease.
  • Chagas C205 series: This series is part of a collaboration agreement made in 2018 with the Drug Discovery Unit of Dundee University in Scotland and GlaxoSmithKline’s Global Health Unit in Spain. With work on the series resulting in a drug candidate for leishmaniasis that will move into translational research, research for a candidate for Chagas from the C205 series is currently on hold.

R&D translation stage iconTranslation

  • Biomarkers: As there is no single reliable test of cure that can be used to monitor treatment effectiveness in chronic Chagas disease patients, DNDi continued work to raise awareness among Chagas stakeholders about the need for biomarkers, with particular emphasis on regulatory aspects and the biomarker development process. DNDi is also supporting the development of a prototype assay for newly identified biomarkers – Apo A1 and Fbn fragments issued from a collaboration with McGill University – together with InfYnity Biomarkers. The analysis of a multi-centre study carried out by NHEPACHA, an Ibero-American network of researchers working on Chagas, is being finalized and will be published in 2020.
  • Fexinidazole: DNDi is evaluating fexinidazole, which was registered to treat sleeping sickness in 2018, as a potential new drug for Chagas disease. This Phase II proof-of-concept study, carried out in five sites in Spain, has been evaluating different short-course regimens of fexinidazole for adults with chronic indeterminate Chagas. The follow-up phase of the study was completed in late 2019; results will be available in 2020.

R&D development stage iconDevelopment

  • New benznidazole regimens: Phase II trial results available in early 2019 showed that all treatment arms were effective compared to placebo and the new regimens presented good safety profiles. The two-week course of treatment with benznidazole monotherapy was particularly promising. While significantly shorter than the standard eight-week treatment, it showed 83% efficacy and none of the patients assigned to this arm had to discontinue treatment due to side effects. Based on these results, DNDi is planning to run an international, multi-site confirmatory Phase III study.

R&D implementation stage iconImplementation

  • Chagas access project: The Chagas Treatment Access project continued to consolidate and expand its activities in the Latin American region in 2019, working with partners in Colombia, Guatemala, Brazil and, since late 2019, Mexico. In Colombia, after two years since the first pilot projects started, the number of people screened in the municipalities of Támara and Nunchía in Casanare state increased from 25 in 2017 to 400 per year in 2019. For those who had access to diagnostic testing, the wait time to receive their results was reduced on average from one year to less than one month. Approximately 20% of people who had access to diagnosis during the two-year period tested positive for the disease.
  • Chagas Clinical Research Platform (CCRP): With around 450 members from over 150 institutions and 24 countries, the Chagas Platform continued work to catalyse the involvement of researchers from endemic countries in improving R&D for Chagas, from drug discovery to implementation.Celebrating the Platform’s 10th anniversary in 2019, members supported the development of products to help decision-making around Chagas research, such as a target product profile (TPP) for immunocompromised patients, a TPP for paediatric Chagas disease, and an algorithm to assess treatment response in primary health care. Members also discussed priorities for research in pre-clinical, clinical, and implementation research needed to contribute to Chagas disease control over the next decade.The Platform also started working to catalyse a prospective cohort to unify the Chagas clinical and research community, an action suggested in the ‘Santa Cruz letter’ developed by the Platform and the Chagas Coalition in 2018 that asked governments to step up efforts to eliminate Chagas as a public health problem. The letter also supported the request for an official World Chagas Day, which was approved by the World Health Organization at its 72nd World Health Assembly in 2019. The first World Chagas Day will be celebrated on 14 April 2020.

Photo credit: Ana Ferreira-DNDi

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by Zrein M, Chatelain E. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 2019, doi: 10.1016/j.bbadis.2019.165628

Summary: Control of Chagas disease is extremely challenging, not least because of a lack of methods to reliably assess treatment efficacy. While there have been impressive efforts in basic research to help with the management of Chagas disease, translation into clinically available products has been lacking. This review is a synopsis of immunological characteristics of T. cruzi and attempts to elucidate what hampers development of methodologies for the unmet medical need of disease monitoring. The authors conclude that it is essential to change the paradigm of serological methods for monitoring parasite clearance: analysing the broad spectrum of antibody diversity is more informative about clinical status than conventional serology tests designed merely for global detection of antibodies.

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