The need for global collaboration to tackle hidden public health crisis of Chagas disease

Abstract

Chagas disease has a unique history where the confluence of rural and marginalized populations affected, the deeply rooted attitudes, clinical practices and an underfunded research area has resulted in one of the most current neglected health issues. Globalization has changed the epidemiology of the disease, which is now found throughout the Americas but also in Europe and Japan. Thus, Chagas disease is a global public health problem. In this new paradigm, a strong partnership aimed to coordinate actions to scale up diagnostics and treatments, to engage communities and health practitioners in implementation and advocating for sustained funding for the development of improved tools, can play a critical role to leave behind this story of neglect. Even with the imperfect tools currently available, still much can be done.

Keywords::

• Chagas disease
• community
• investment
• research

Chagas disease (American trypanosomiasis) is a little-known but debilitating and potentially deadly infectious disease highly prevalent throughout the Americas, where Chagas is the leading parasitic killer and predominantly affects poor and marginalized populations. Caused by the Trypanosoma cruzi parasite, Chagas disease is one of the 17 neglected tropical diseases (NTDs) listed by WHO.

T. cruzi can be transmitted to humans in several ways. Transmission through a vector, the triatomine bug, has historically been the most important route of transmission and continuous reinfection in all endemic areas, until plans for vector control were carried out. Similarly, T. cruzi transmission via blood transfusion was handled quite well in endemic countries. The control of these two ways of transmission has left the mother-to-child transmission route as the most important, not only in endemic countries, but also in countries receiving Latin American immigration [1]. Also, observations of outbreaks of oral transmission in endemic countries through food or drinks contaminated by the feces of the parasites or by the parasites themselves have recently accumulated [2].

Furthermore, the drugs available to treat Chagas disease – nifurtimox and benznidazole, which were developed through veterinary research in the 1960s – are limited in terms of efficacy and safety. Both drugs have the highest efficacy in early infection, but when infected individuals are untreated, the infection becomes chronic and between 30 and 40% of them will have chronic cardiac, digestive (megasyndromes) or neurological complications responsible of morbidity and mortality, years after the infection [3,4]. Additionally, they must be administered for long periods of time (2 months) and under medical supervision as they are associated with serious adverse effects.

Treatment of Chagas infection has been hampered, unlike other illnesses, by the paramount importance given to the autoimmune theory of the disease that has prevailed for many years. As a result, several generations of doctors and nurses were trained in the belief that Chagas disease had no treatment. In fact, currently, most chronic infected people are not treated with specific antiparasitic drugs, and the research for new and better drugs have been slowed or forgotten for years, until very recently [5]. Nowadays, the role of the parasite persistence in the pathophysiology of Chagas diseases is recognized [6], as well as the need for specific treatment [7]. Moreover, treatment has been considered as a strategy for a secondary prevention in order to prevent clinical development of disease after the infection [8].

Officially, between 8 and 10 million people are infected by T. cruzi, causing 10,000 deaths each year [3], but other estimates significantly increase these numbers [9]. In addition to this, it is estimated that up to 90 million people are theoretically at risk of infection. Chagas disease also has a significant economic impact. Recently, a computational study showed that the global costs for Chagas disease are US$7–19 billion per year, similar or even higher to those of other important diseases such as rotavirus or cervical cancer [10].

As it is the case for other NTDs, the fight against Chagas has been mainly focused on control and transmission, with very little attention aimed to scaling up and/or improving the therapeutic options of those already affected. Noteworthy, in the past 25 years, there have been major advances in the control of Chagas disease in endemic countries. Multinational initiatives on vector control have obtained good outcomes, in a clear and successful strategic collaboration and coordinated effort toward a clear objective [11].

Historically, very few resources have been invested to study Chagas disease or to provide care to the millions of people affected, namely, global funding for Chagas R&D in 2012 was US$31.7 million, which represents scarcely 1% of total R&D funding spent on neglected diseases globally. Investment has been essentially steady over the last 5 years and relies largely on public funders, which have contributed with almost three-quarters of the investment, while philanthropic organizations and the pharmaceutical industry contribute to a much lesser extend [12].

Most of those affected by Chagas disease live in rural areas or peri-urban slums and have little political voice. As a result, millions of them are still receiving inadequate care despite the recommendations of WHO [13], and millions of patients have not yet been properly diagnosed or treated.

The specific treatment for Chagas disease is far to be ideal, but recently published research shows clear benefits in patients taking antiparasitic drugs [14]. So, even if continued efforts are needed for the development of new drugs, more accessible and with a lesser toxicity, there is a window of opportunity to scale-up treatment with the available one. To achieve this goal, both patients and professionals have to be engaged and educated on the benefits of the specific treatment. In this sense, the implementation of a pharmacovigilance system could contribute significantly to improve the training of health practitioners and accelerate the scaling-up of the specific treatment. Prerequisite is that national health systems confront their organizational challenges enabling better coordination among the existing congenital and transfusional control programs and their assistential networks so that both case detection and effective care can be upgraded. Despite the epidemiological data already available, effective vertical transmission control programs are not in place neither in endemic nor in non-endemic countries and, especially in the latter, there is no clear and forceful legislation that regulates blood transfusions or organ transplantation [Requena-Méndez A, Albajar-Vinas P, Angheben A, et al.; Chagas Disease European Working Group. Health policies to control Chagas disease transmission in European countries: a 2013 update (2013), Submitted].

Another challenge that undermines progress against Chagas disease control is the availability of benznidazole, the first-line drug for treating Chagas disease. Recent events of stock shortages or run outs of benznidazole have not only left Chagas patients without treatment, but also have cut positive dynamics to engage them in the whole treatment process. In addition, in non-endemic countries, Latin American migrants potentially affected by Chagas disease can find themselves in a precarious situation, as access to healthcare in recipient countries is being increasingly questioned [15]. The lack of early biomarkers of therapeutic efficacy is yet another critical obstacle for the scaling-up of the antiparisitic treatment within health systems. In this regard, some new initiatives have been developed in recent years, but there is still a need for a continued and sustainable financial commitment by funders so that one of the highest priorities for research in Chagas disease can be tackled.

We can conclude that the confluence of a disease with a long asymptomatic phase, clinical symptoms not clearly perceived as a consequence of the infection and affecting marginalized populations has resulted in a silent public health crisis. Even with the imperfect/suboptimal tools available now, it is possible to screen people at risk and treat the disease at the community level. Control strategies in non-endemic countries need to focus on preventing congenital transmission and infections transmitted through blood transfusions and organ transplantation.

However, this requires prioritization and mobilization of resources, to strengthen health systems capacities and to improve communication with affected populations. Such a public health approach requires a high dosage of political will to reformulate health systems allowing to implement sustainable Chagas disease surveillance programs, which are not yet in place in a number of endemic and non-endemic countries.

To pursue this ambitious goal, several outstanding stakeholders covering the whole spectrum of Chagas disease, from research and development to assistance or advocacy, have joined efforts to create an international coalition [16], promoting a patient-centered agenda focused in scaling-up access and treatment, resource mobilization for sustained investment in innovation and rising public and policy awareness to remove Chagas from the list of neglected diseases.

The Uniting to Combat Neglected Tropical Diseases initiative launched in 2012, where a community of international partners endorsed the London Declaration on Neglected Tropical Diseases on the occasion of the launch of the WHO 2020 roadmap for accelerating work in NTDs [17], has positioned the NTDs to the top of global political agenda. The initiative that calls for coordinated efforts to eliminate or control 10 NTDs, including Chagas disease [18], presents an unprecedented opportunity to direct the focus of multiple stakeholders (from governments to WHO) to key areas where actions could have considerable impact including resource mobilization to find next-generation treatments and interventions for the affected populations.

In this new paradigm for NTDs, there are several drivers for the urgency and a need of a strong collaborative action to our success in combating Chagas disease. First, WHO has created a policy recommendation [13] calling for the treatment of asymptomatic patients. How to best implement this treatment remains challenging. Second, there are now better estimates of both disability-adjusted life years (800,000) and economic impact (US$627.46 million in healthcare costs) of Chagas disease infection and comorbidities. This adds the economic rationale on top of the ethical rationale for engagement and impact. Third, the scope of the Chagas problem has more clearly evolved as information has improved, and increases in migration and population movements have changed the epidemiology and geographic distribution of the disease that is not anymore entirely confined to Latin American countries, but also found in the USA, Europe, Australia or Japan. A strong partnership that sets a global framework for coordinated action can be a critical step in catalyzing progress toward the long overdue task of Chagas disease control by improving and scaling-up treatment. The Global Chagas Disease Coalition seeks to achieve this vision.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.