Frequently Asked Questions
1. What is Chagas disease?
Chagas disease is parasitic disease transmitted primarily by large, blood-sucking reduviid insects widely known as "the kissing bug." The disease is endemic in 21 countries in Latin America, where approximately 8 million people are infected. Without an adequate diagnosis and treatment, one in every four Chagas patients develops a fatal symptom of the disease, usually swelling of the heart muscle.
2. When was Chagas disease discovered?
Chagas disease and the complete life cycle and shape of the parasite were first described in 1909.
3. Where was Chagas disease discovered?
In Lassance, a small town in the country side of Minas Gerais state, Brazil.
4. Who discovered Chagas disease?
Chagas disease was discovered by Carlos Chagas, a Brazilian researcher working for the Instituto de Manguinhos (now know as the Oswaldo Cruz institute) in Rio de Janeiro, Brazil.
5. What led Carlos Chagas to the discovery of Chagas disease?
In 1909 malaria was devastating the area north of Minas Gerais, Brazil, making the extension of the 'Central do Brasil' railway impossible. Carlos Chagas, then a young scientist, was sent to Lassance, to help in the fight against malaria. In doing so he observed the first human cases what would later be named "Chagas disease" after his discovery.
6. Why was the protozoan of the Chagas disease named Trypanosoma Cruzi?
The name Trypanosoma Cruzi is a tribute to Carlos Chagas' mentor, Dr. Oswaldo Cruz.
7. How old is the Chagas parasite?
Recent archaeological studies have found Chagas parasites Latin American humans from 9,000 years ago.
8. Where is Chagas disease endemic?
Chagas disease is endemic in 21 countries across Latin America. Patient numbers are growing in non-endemic, developed countries (including Australia, Canada, Japan, Spain, Italy, France and the United States) due to increased population movements.
9. How is Chagas disease spread?
Over 80% of Chagas cases are transmitted by vector, meaning spread by insects. The Chagas disease vectors are blood-sucking triatomines, a subfamily of reduviid insects more commonly known as "kissing" bugs in English, "vinchucas" in Spanish speaking Latin American countries, or "barbeiros" in Brazil. In Latin America, 41,2008 new cases are estimated to occur yearly due to vector transmission, with highest numbers occurring in Bolivia and Mexico, with an estimated 10,300 and 7,700 new cases per year, respectively. Approximately 15 % of cases are transmitted by blood transfusions or organ transplants, 4% by congenital (mother-to-child) transmission, and less than 1% come from lab accidents or the ingestion of contaminated foods.
The bug was nicknamed 'barbeiro' (which means 'shaver') due to its preference to bite on the face while people were falling asleep.
10. How many people are at risk in endemic areas?
In Latin America, currently about 100 million8 people are at risk, which represents approximately 18% of the entire Latin American population. The countries with the most people at risk are Mexico (29.5 million) and Brazil (21.8 million).
11. How many women between the age of 15 and 44 are infected and why is it important to know this number?
In Latin America, it is estimated that 1,809,5078 women of childbearing age (15 to 44 years old) are infected with Chagas disease. Prevalence rates of asymptomatic women range from 5%-40% in endemic countries, with highest total absolute numbers observed in Brazil (460,000), Argentina (275,867), and Mexico (243,000). These numbers are important because congenital transmission occurs in up to 12% of pregnant women who are infected with T. cruzi.
12. What is the public health challenge in relation to congenital infection?
Successful efforts in controlling vector transmission of Chagas disease do not reduce congenital transmission of women infected with T. cruzi who are of childbearing age. There is a consensus that congenital T. cruzi infection will be a pressing public health problem for at least for the next 30 years, until the population of infected women of child bearing age decreases to insignificant levels, at least in the Southern Cone countries. Mother-to-child transmission of T. cruzi has all the characteristics required to be a public health priority, as it is relatively frequent, severe, identifiable, and treatable.
13. How many children are born infected with Chagas disease due to congenital (mother-to-child) transmission per year?
Every year, an estimated 14,3858 children are born infected with Chagas disease. The countries with the highest absolute numbers are Brazil, Argentina and Bolívia with 5,000, 1,800 and 1,500 new congenital cases occurring every year.
14. How can congenital (mother-to-child) transmission be prevented?
Screening of pregnant women for Chagas disease during pre-natal health care, especially when they are born in an endemic area, has the potential to prevent significant disease burden. The screening of newborns to verify if they have been infected should be prioritized in order to treat cases as early as possible. The earlier the treatment is initiated, the higher the chances of treatment success.
15. What organs are affected by the Chagas disease?
Chagas disease most commonly affects the heart, esophagus or intestines, but respiratory, urinary and central nervous system (CNS) complications have also been recorded.
16. What are the phases of Chagas disease?
Chagas disease has three phases: acute, indeterminate (asymptomatic) and chronic (symptomatic) phases.
17. What are the signs and symptoms of the Chagas disease?
The acute phase often goes undetected because it can be asymptomatic. Symptomatic acute Chagas disease is often characterized by non-specific symptoms such as fever and malaise, which resolve on their own in four to six weeks. A common sign of the acute phase is swelling of the eye lid (known as Romaña's sign), which is a reaction to the parasite after a triatomine bite.
The indeterminate phase is asymptomatic and may last up to 30 years. Chronic symptomatic disease develops in 10% to 30% of infected patients
and most often involves complications of the heart and/or gastrointestinal tract, depending on geographical location or parasite strain. Chagas disease is a leading cause of infectious cardiomyopathy worldwide.
18. What is the estimated number of people infected with the Chagas disease in Latin America?
The estimated number of people infected with Chagas disease in the 21 Latin American disease enedmic countries is approximately 8 million. The countries with the highest number of infected individuals are Brazil (1.9 million) and Argentina (1.6 million). However, the countries with highest prevalence rates (by any transmission route) are Bolivia (6,75%) and Argentina (4,13%).
19. How do these figures compare with other infectious diseases?
An estimated 2 million people are living with HIV/AIDS in Latin America, which means that the estimated number of people infected with Chagas disease in the region is four times that of HIV/AIDS in Latin America and the Caribbean.
20. How many people die due to the Chagas disease per year?
Causing 14, 000 deaths annually, Chagas disease kills more people in Latin America than any other parasitic disease, including malaria. In the Americas, Chagas disease causes more deaths per year than Hepatitis C (8,000), Hepatitis B (5,000), Malaria (2,000) and Dengue (2,000).
21. What is the economic impact of the Chagas disease?
Chronic Chagas disease results in significant disability with great social and economic impact, including unemployment and decreased earning ability. In Brazil alone, losses of over US$ 1.3 billion in wages and industrial productivity were due to workers with Chagas disease. In addition to the loss in productivity, the medical costs to treat infected individuals who develop severe cardiac or chronic digestive problems is several times this amount.
22. What is the estimated number of people infected with the Chagas disease in non-endemic countries?
Patient numbers are growing in non-endemic and developed countries due to increased population movements. In 2007, approximately 14 million people from Chagas disease endemic countries were living in non-endemic countries. A 2006 study estimated that between 96,631 and 700,712 people may be infected in Australia, Canada, Spain and the United States alone.
Australia (2005-6) - 1,067 Canada (2001) - 1,218 Spain (2003) - 6,125 United States - 71,970 - 676,051
23. Is there a cure for Chagas disease?
Treatment with benznidazole and nifurtimox drug is curative only in acute or early chronic infections, and in congenital cases. In general, treatment efficacy in the acute phase is 60-85%, and for congenital infection it is 90% when treated in the first year of life. Complete cure can be expected with immediate treatment of accidental infections.
Few studies support the use or benznidazole for chronic complications of Chagas disease. BENEFIT, a TDR-supported trial, is expected to fill this knowledge gap for the use of benznidazole.
24. Have there been any new treatments developed for Chagas disease since the 1960s?
25. How are the drugs administered to the patients?
Benznidazole: Patients generally receive two or three daily doses for a period of 30 - 60 days.
Nifurtimox: Treatment regimen is for 60-90 days, and also divided in two or three daily doses.
There is no curative treatment for chronic symptomatic disease. In this phase, patients usually receive palliative drugs.
26. What are the current treatments available for children?
Neither benznidazole or nifurtimox is currently available in a pediatric formulation. DNDi is developing a paediatric tablet of benznidazole, in partnership with Laboratório Farmacêutico do Estado de Pernambuco (LAFEPE), a Brazilian public health institution.
Infants and children are currently treated by dividing a 100mg adult benznidazole tablet in up to 12 pieces, by crushing the pill fraction and diluting it in water, juice or milk. This practice risks making the treatment inefficient and unsafe due to variation and imprecision in drug dosing.
27. What are the limitations of the current treatments?
The limitations of current treatments are the long treatment period (30, 60, or 90 days), the toxicity of the drug, extreme side effects and the lack of a pediatric formulation. These limitations cause high rate of patient non-compliance.
28. What are the side effects of the current drugs available?
Benznidazole: The main side effects of benznidazole are skin inflammations, which occur between the seventh and tenth days of treatment, often associated with swollen or enlarged lymph nodes.15 Reduced motor and sensory function is dose dependent and usually occurs after the 6th week of treatment. Other observed side effects are nausea, headache, blood disorders , fever, muscle pain, and joint pain.
Nifurtimox: The most common side effects are digestive: abdominal pain, nausea and vomiting, loss of appetite, weight loss. Psychiatric disturbances, inflammation of the nervous system, and decreased white blood cell counts may also occur.
29. Is there a treatment for the chronic phase of the Chagas disease?
A number of experts now recommend treatment of adults in the indeterminate stages of T cruzi infection, who are in the absence of advanced Chagas cardiomyopathy. The BENEFIT trial (BENznidazole Evaluation For Interrupting Trypanosomiasis') is currently under way, and should help clarify treatment decisions for this group of patients.
30. Do the drugs available kill the parasite effectively?
Parasitological cure is thought to occur in 60% to 85% of patients in the acute phase and in more than 90% of congenitally infected infants treated in the first year of life. Efficacy is lower as the time of infection advances in chronic disease, and tools to evaluate parasitological cure at chronic phases are limited.
31. Do all infected people receive treatment?
No. The reported number of patients treated for Chagas disease remains extremely low. The lack of affordable medical tools for diagnosis and treatment that are adapted to the rural conditions where Chagas is most common greatly hinders effective patient care and management. In fact, the number of Chagas patients treated in non-endemic countries such as Spain, Switzerland and the US are comparable to, and sometimes greater than, the number of patients reported to be treated in disease-endemic countries like Mexico or Colombia, where the vast majority of infected patients live.
Benznidazole, the most common treatment for Chagas disease in Latin America, is most effective (and less toxic) in children and adolescents. There is no accepted treatment program for the millions of adults infected with chronic Chagas disease.
32. What diagnostic tools exist for Chagas disease?
Diagnostic tests are the include:
Rapid diagnostic test (RDT) - STATPAK: Used as a screening tool by MSF and control programs in the field.
HAI: indirect hemaglutination.
ELISA recombinant: the difference with the ELISA conventional is the use of recombinant antigens instead of a purified one.
IFI: indirect immunofluorescence.
33. What are some limitations and difficulties of the current diagnostic tools available?
Diagnosis of Chagas is a complex procedure involving not a single test but a combination of several serological tests. Usually two initial tests are performed. If they disagree, a third serological test must be done in order to obtain a final diagnosis. The available diagnostics tests, with the exception of RDT STATPAK, are often not suitable for the poor, rural communities where Chagas disease is most commonly acquired. These communities lack the financial, physical and skilled human resources to conduct such tests. Shear distance from established testing sites is also often a barrier to access.
Due to the lack of efficient diagnostics, the number of cases is assumed to be greatly underreported. Infections are usually discovered in the chronic phase, when treatment is most challenging. The research and development for new diagnostic tools has been limited.
34. What improvements are needed to diagnose better patients with Chagas disease?
An affordable, easy to use rapid diagnostic test with acceptable sensitivity and specificity is badly needed for Chagas disease. Such a test would make testing in every rural and remote location (without the need for existing laboratories and skilled lab technicians) possible.
Currently available tests also need to be simplified, as the ELISA, HAI and IFI take approximately 2- 3 hours to obtain results and often require one lab technician to focus solely on Chagas diagnosis. In cases where this is not possible, patients do not get tested.
There is an urgent need for laboratory research to identify new markers of Chagas and develop new technology specially related to the test of cure.
35. What are the current patient treatment needs?
Two immediate needs exist. First, a pediatric strength treatment which is affordable, age-adapted, safe, and efficacious. Second, a new drug for the chronic stages of the disease that would ideally also be effective in every stage.
36. What is DNDi doing to address unmet treatment needs?
In the short term, DNDi and LAFEPE are working together to develop a pediatric formulation of benznidazole, which will be available in 2010. DNDi is also working on clinical development of azoles and other combinations.
In the long term, DNDi is focusing on new drugs and improved research & treatment capacities. By 2014, DNDi aims to make available one new pediatric strength treatment and have one new drug registered from its Chagas-specific portfolio..
37. What is DNDi's role in the R&D for Chagas disease?
DNDi is currently the only product development partnership with a research agenda for Chagas disease. The absence of a profitable market for Chagas drugs necessitates the development of innovative mechanisms to stimulate and finance R&D, as well as serious political commitments to foster an environment that encourages and pushes research innovation for Chagas.
38. How much is invested in R&D for new drugs to treat Chagas disease?
Of the neglected diseases, Chagas disease is among the diseases that receive the least investment for R&D. In 2007 only about US$10 million of the US$2,560 million R&D investments for neglected diseases went to Chagas disease.
39. To which phase of research is the majority of funding allocated?
Of the approximately US$10 million in R&D investments in Chagas disease in 2007, only 10% was allocated to drug development.
40. What is the reason for the lack of R&D on treatment and diagnostics?
The main reason for lack of R&D is the lack of funds. Some research laboratories might have good initiative but most of them are stymied because funding is limited.
The second factor is the poor access to diagnosis and treatment. National control programs tend to focus on screening for congenital and blood transfusion transmission, rather than diagnosis and treatment.
41. How can R&D be boosted?
Governments can do much to change the current landscape, to ensure international cooperation between public and private actors, and to mobilize tremendous resources for medical research and development .
42. How difficult is it to find partnerships?
The key factor to find partnerships is to be able to bring together individual, public, and private actors, regardless of their different motivations. One of the main principles in these partnerships is to share a common needs-driven objective with the actors from these different spheres. To this end, DNDi's partnerships with donors, including governments, international organizations, non-governmental organizations, private foundations and individuals, play a major role. Today DNDi manages 250 research, technical, and funding agreements with both public and private partners across all diseases that we work with. However, the successful conclusion of these agreements also depends on solving critical issues, such as licensing rights, confidentiality, intellectual property rights management, and lack of profitability.
43. How does a new drug get registered?
There is no international regulation regarding the registration of drugs and therefore it differs from country to country. In general, it is a long and complex process, involving elaborate documentaion and compliance to stringent quality standards. Adoption of a new drug can be a very slow prcess.
44. What has to be done to make the new drugs accessible to the most neglected patients?
The first step for patients to access treatment requires identifying and reporting the Chagas disease cases, critical today as actual cases are significantly under-reported. In addition, there needs to be consensus on treatment guidelines, training of health workers, and finally, the political will to address the problem.
In parallel, it is essential to ensure a continuous, affordable supply of drugs. This requires agreements from drug manufacturers whereby they commit to manufacture the product over the long term and sell it at an affordable price. In order to ensure affordability, maufacturers must be able to obtain active pharmaceutical ingredients at the lowest cost possible. In addition, medicines need to be distributed via a reliable supply chain to health centers that may be in very remote, rural areas.
In the mid to long term, it will be important to monitor treatment safety and efficacy in large Phase IV trials, and to update treatment guidelines accordingly.
45. Why is Chagas disease considered a "silent" disease?
Chagas is called a silent disease for three reasons:
First, because major actors such as Latin American governments, pharmaceutical companies, international bodies and civil society (non-government organizations) have not done enough to solve the problem of Chagas disease.
Second, Chagas is called a silent disease because the people infected rarely show the symptoms of infection. Around one third of them will actually develop the disease. Then, very often the victim dies without even knowing the exact problem.
Finally, patients are generally socially, politically, and economically disenfranchised due to poverty and remoteness, with little or no political voice.
46. Why is there so little political interest?
The interest in the political world has largely been on vector control programs, with little interest or even acknowledgment of the need to treat patients.
47. Where have efforts been put at national level?
National government efforts have been put on prevention activities, such as vector control. The need for new treatments and diagnostics is starting to be acknowledged.
48. Why are so few pharmaceutical companies interested in Chagas disease?
Chagas disease mainly affects the poorest communities in Latin America, which do not represent a profitable market for pharmaceutical companies.
49. What is the social-economical profile of the patients with the Chagas disease?
The poorest of the poor. Most live in remote rural areas with limited access to healthcare and education.
50. Why do we not have a medical consensus on treatment with the existing drugs?
Current therapy for Chagas disease is limited to two drugs, nifurtimox and benznidazole, which are primarily used to treat acute and early chronic infections in children. The evidence with regards to treatment of adults and the indeterminate stage is conflicting, and there is no available evidence to support therapeutic use for symptomatic chronic disease. Even in children, who are known to better tolerate treatment with these compounds than adults, the cure rate is only around 60-70%.
51. What has DNDi done to address the lack of medical consensus with regards to Chagas treatment?
DNDi organized a set of meetings in 2006 to seek advice from experts on specific needs for new treatments in order to develop a drug development portfolio for Chagas' disease. Since then, DNDi has worked to strengthen its Chagas portfolio, and is conducting research in all the phases of drug development for Chagas disease. In the short term, DNDi and LAFEPE are working together to develop a pediatric formulation of benznidazole, which will be available in 2010. DNDi is also working on clinical development of azoles and other drug combinations.
52. What is the role of the WHO and the PAHO in the fight against the Chagas disease?
The role of the WHO and PAHO is to increase rapid-response health interventions to control and eliminate neglected infectious diseases, to strengthen national and local health systems, particularly information systems, and to adopt intersectorial and interprogrammatic approaches to address the social determinants underlying these diseases.
PAHO is expected to play a fundamental role through its ongoing work in mapping the incidence of these diseases in the Americas. The mapping helps pinpoint problems with greater precision while identifying gaps in information and action. PAHO will also spearhead technical cooperation efforts and provide expertise to support the development of national and local plans for control and elimination of these diseases.
53. Why is the patient's mobilization around the Chagas disease so weak?
As Chagas disease primarily affects people from poor, rural and remote areas across 21 endemic countries, it is difficult for patients to collaborate and form the critical mass needed to develop a strong political voice.
54. Are medical staff in endemic and non-endemic areas prepared to treat Chagas disease?
No. Chagas disease is minimally in medical training programs. As a result, only a small number of doctors have adequate knowledge of Chagas disease.
55. What causes Chagas disease to be called a vicious cycle?
First, as current estimates of Chagas disease prevalence rates are based on incomplete data, the scope of treatment needs is not evident. Without up-to-date, evidence-based reporting of disease prevalence and patient needs, there is little incentive to engage in research and development for new drugs and diagnostics. Investments to support targeted epidemiological studies are needed to generate a more accurate estimate of Chagas disease prevalence and incidence in Latin America, which can then stimulate the development of new health tools for Chagas disease.
The second vicious cycle refers to the cycle of poverty. Chagas affects predominantly poor populations, and results in significant disability that often leads to unemployment, decreased earning ability and increased costs in order to access treatment. As a result, Chagas disease patients often remain poor and they and their families continue to live in conditions that promote the spread of the disease and perpetuate this cycle.
56. What has to be done in 2009?
In 2009, as we mark the 100th anniversary of the discovery of the disease by Carlos Chagas, we must take advantage of the political momentum surrounding the disease and create an opportunity to raise awareness about the challenges facing Chagas patients. The imbalance between the disease burden and the priority level on the global health agenda must be redressed.
DNDi offers one possible solution to the lack of safe, effective, affordable and adapted drugs for Chagas patients. But in order to move the plight of Chagas patients to the top of the global health agenda, a much larger movement, encompassing the public sector, private industry (pharma, biotechs), philanthropists, academia, international organizations (WHO, PAHO) and NGOs is needed. New initiatives must be also developed and funded now in order to yield positive results in the years ahead, and to end the cycle of neglect for Chagas patients.