Amid the pandemic, Chagas disease continues in search of visibility

Less than 10% of people with the disease in the Americas are diagnosed, and only about 1% of those affected receive antiparasitic treatment

Although in a year COVID-19 has overcome historical marks of diseases caused by infectious agents in the last four decades, like Chagas disease, this neglected tropical disease (NTD) remains as a huge challenge to public health and economic development in some of the most vulnerable areas in the world. Historically relegated by both decision makers and the pharmaceutical industry, it is the most lethal parasitic disease in Latin America, causing 14 thousand deaths each year. According to the World Health Organization (WHO), Chagas disease is one of the NTDs that affects 1.7 billion people worldwide, mainly in poor countries.

The WHO estimates that, of the more than 6 million people with Chagas disease, less than 10% are diagnosed and, of these, very few receive the treatment they need. For 30% to 40% of the infected people, the disease progresses to an end stage of the chronic phase. Of these, most will suffer cardiac damages, often resulting in sudden death or progressive heart failure. The disease can also cause a growth in the gastrointestinal tract and gastrointestinal organs and motor disorders.

Currently, there are only two treatments available to treat the disease: benzonidazole or nifurtimox, both developed decades ago with a long treatment period, 60 days (8 weeks), and frequent side effects, especially in adults. It is estimated that up to 20% of the patients abandon treatment due to these side effects, representing an important barrier to starting treatment. The implementation of shorter treatment can help the implementation of treatment on a large scale and renew hope for people affected by the disease. With that in mind, the Drugs for Neglected Diseases Initiative (DNDi) carried out a randomized, double-blind, phase 2, clinical study, with the objective of evaluating the efficacy and safety of new benzonidazole regimens in the treatment of adults with chronic undetermined Chagas disease.

Our results suggest that the shortest 2-weekregimen maintains efficacy similar to the current standard regimen (8 weeks), with superior safety – no patient experienced serious adverse events or adverse events that led to treatment discontinuation, explains Dr. Fabiana Barreira, Manager of Clinical Trials for Chagas Disease at DNDi. Also, according to her, the next step is the confirmation of these results in a phase 3 study, a broader study, which is already being implemented by DNDi along to other partners. If the effectiveness of the 2-week treatment is confirmed, it will facilitate patient compliance, improving access to treatment, in addition to contributing to the reduction of demands and costs with health. Check here the article published in The Lancet entitled  “New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial”

Silent killer in Mexico

The majority of those infected in Mexico are never tested or treated, which puts them at risk for an enlarged heart and sudden death. Some have lived with Chagas for decades without symptoms, academics revealed in a report published in Reuters. Also, according to the publication, the pandemic slowed Mexicos already limited tests and the number of diagnoses dropped by more than half in 2020 compared to 2019, when COVID-19 overburdened the health system. Gustavo Sanchez, head of the National Center for Preventive Programs and Disease Control (CENAPRECE), attributed the drop to the delay of chronic patients in seeking help and to the smaller number of people donating to blood banks, where the examination detects many of the cases. He also said that the governments ability to process the tests has been reduced. We cannot deny that the diagnostic work, not only for Chagas, but for other diseases, was affected by the pandemic, he said in the report.

The article published in Reuters also highlights that between 2003 and 2020, the Mexican government confirmed only 11,980 cases of Chagas, according to data obtained through a request for freedom of information. However, academics estimate that the country has between 1 and 2 million cases, numbers that the government rejects. The article also says that in 2020, the number of people treated fell to just 391 – was over 850 in 2018 and 2019, according to the government. In the report, Sanchez said the government will soon begin testing children and women of childbearing potential in 78 high-risk areas to find new acute cases, and broader tests to find all chronic cases would not make epidemiological sense. Check out Mexicos Epidemiological Bulletin Number 10 | Volume 38 | Week 10 | From March 7 to March 13 2021.

Main challenges of Chagas disease

Diseases like Chagas were already neglected before COVID-19. Now, new challenges are imposed on the fight against this and other NTDs due to the destination of resources for the fight against the pandemic, the pressure on health centers, the fear of patients to contract the coronavirus and the still limited knowledge about the interaction between diseases and drugs used in treatment. Dr. Sancho, Coordinator of the Global Coalition of Chagas Disease, recognizes that after a time when there has been a lot of progress in vector control, it is now a question, in addition to maintaining this effort, to achieve similar advances in access to comprehensive care for people affected. “Right now, it is estimated that access to treatment for people who may be affected is very low (some estimates mention just 1%). In countries where the impact is estimated at hundreds of thousands or millions of people, the rate of people treated is extremely low. Along with access, control of other routes of transmission, such as mother-to-child, is vital. There is a worldwide consensus to be more committed to actions to control vertical transmission, expanding the diagnosis for women of childbearing age and children, since the treatment is highly effective at these ages with early detection”, he points out. The diagnosis of Chagas along with diseases such as HIV or syphilis in the activities of the health system is one of the major advances proposed, as presented in the Elimination of mother-to-child transmission (EMTCT) strategy together with the Pan American Health Organization (PAHO). And it is aligned with the approach of integrating NTDs at all levels of the health system.

The eradication of the disease by 2030 is one of the WHOs goals. However, the eradication or even the reduction of NTD cases necessarily involves understanding the infectious agents and developing safe, effective and accessible drugs and vaccines. For that, investment in research and development is essential, but unfortunately, in the 21st century, no innovative medicine was produced for any of the 20 neglected tropical diseases.

In January, WHO set global goals to eradicate 20 NTDs, including Chagas disease, by 2030, with governments committing to support efforts that have led 42 countries to eradicate at least one NTD in the past decade. However, experts warn that the pandemic could reverse some of that progress. For Dr. Sancho, this roadmap approved by the WHO member countries has a very difficult starting point. “First of all, it is important to note that this roadmap, with its objectives and goals, and its change of focus is very ambitious, in a positive sense. It implies integrating NTDs into the routine of the health system, with a much more transversal and comprehensive approach. But it is the countries that need to find out how to apply it, as well as the resources needed to do so. And therein lies the problem: the roadmap was designed in a world where the pandemic had not yet entered and was approved in the midst of a pandemic. The plan establishes some revision phases (the first in 2023)”, he observes. In his opinion, what is clear is that the starting point is not the same for neglected diseases like Chagas, as we see a serious setback in the advances made before 2020. “I think the goals and expectations would have to be readjusted”, he says.

Also, according to the Coalition coordinator, for the measures proposed by WHO to be implemented, there is a lack of commitment and willingness by political authorities, financiers and also civil society, as well as resources to fund these commitments. It is also necessary to facilitate the access of the affected people to the instruments of control, diagnosis and treatment currently available, as well as to the new ones that are being investigated. And lastly, keep in mind that countries are ultimately the ones that should take leadership on the roadmap and adapt it to their context with the collaboration of all stakeholders (first, populations at risk, in addition to experts and local and global organizations).

Chagas in times of COVID-19

At the beginning of the pandemic, the Chagas coalition released a guide of recommendations with the little evidence that there was at the time for Chagas disease. Subsequently, in a joint publication with several members of the Coalition, the implications of COVID-19 for people living with Chagas were studied in more detail, highlighting the greater lethality of the coronavirus in the population with Chagas heart disease and greater risk of prevalence in marginalized groups, among other factors. The information can be accessed here: https://globalheartjournal.com/articles/10.5334/gh.891/.

“With regard to the global fight against disease, if there is anything positive about this pandemic, it is the increasingly shared awareness that there is not a single disease that we should leave without care or a single person without care. No disease is an island, copying the phrase by author John Donne. Everyone is part and responsibility of all mankind. The consciousness of the importance of being more involved in global health is greater than before the pandemic”, admits Dr. Sancho. For him, hopefully, this awareness also benefits NTDs that tend to affect mostly neglected populations.

Finally, the Coalition coordinator recalls that advances and work carried out during the pandemic in different parts of the world deserve recognition. “Despite the reduction in personnel and budget, in addition to the limitations of mobility and personal attention imposed by COVID-19, it has been possible to continue to maintain activities, although somewhat reduced, in many locations. This gives great hope for driving the progress of the disease, which has gained more visibility since the approval of World Chagas Disease Day in 2019, by WHO. Now, we need the commitment to translate into greater well-being for the people affected and populations at risk”, he concludes.

World Day to Tackle Chagas Disease

The International Federation of Associations of People Affected by Chagas Disease (FindeChagas) chose April 14 as “International Day for People Affected by Chagas”, due to the symbolism of this day. The date has been used by FindeChagas to demand better strategies for coping with the disease. The creation of a World Day was presented to WHO member states as a historic opportunity to transform the reality of millions of people, their families and communities. FindeChagas was officially created in October 2010 and is made up of more than 20 associations worldwide (Argentina, Australia, Bolivia, Brazil, Colombia, Spain, United States, Italy, Mexico, Switzerland and Venezuela).

The date is also important because it refers to the day when Carlos Chagas, in the small Minas Gerais-state town of Lassance, made the first diagnosis of a human case of the disease caused by Trypanosoma cruzi (described by him in 1908). April 14 is an opportunity to think about Brazilian science and the people affected by Chagas disease and other NTDs that mainly affect neglected populations. It is a day to remember the past, looking at the present and the future.