Overview: Project Chagas
One of the main reasons Andrew and I came down to Bolivia was to do a research project on Chagas disease.
What is Chagas Disease?
Chagas disease is a parasitic illness endemic to most of Latin America that affects over 14 million people worldwide. The parasite is called Trypanosma cruzi (a cousin of the parasite that causes African sleeping sickness), and the vector is a beetle-like insect called the reduviid bug, or as Bolivians call it, the vinchuca.
This nocturnal insect lives in dark, dry places such as the cracks in the walls of adobe mud houses, which most of Latin America’s poor inhabit. The insect comes out at night to feed on human or animal blood, and sleeping humans, often children, are frequent targets. After the vinchuca bites the person and has a blood meal, it defecates near the site of the bite. Parasites from its stomach are passed through the feces and onto the person's skin. Infection occurs when the person scratches or accidentally rubs the parasite-containing feces into the bite wound, allowing trypanosomes to enter the bloodstream. Oftentimes, however the bite itself can be asymptomatic; as such, many people are unaware of the moment when they become infected.
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A T. cruzi parasite hanging out among red blood cells (www.taringa.net) |
This nocturnal insect lives in dark, dry places such as the cracks in the walls of adobe mud houses, which most of Latin America’s poor inhabit. The insect comes out at night to feed on human or animal blood, and sleeping humans, often children, are frequent targets. After the vinchuca bites the person and has a blood meal, it defecates near the site of the bite. Parasites from its stomach are passed through the feces and onto the person's skin. Infection occurs when the person scratches or accidentally rubs the parasite-containing feces into the bite wound, allowing trypanosomes to enter the bloodstream. Oftentimes, however the bite itself can be asymptomatic; as such, many people are unaware of the moment when they become infected.
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| The vinchuca bug. Can't keep its poop to itself. |
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| This adobe house (on the L) in the village of Potolo is the perfect hideout for Vinchuca bugs |
There are 3 phases of Chagas disease:
In the acute phase, the patient may experience swelling at the site of the vinchuca bite, fever, fatigue, or lymph node swelling. When the swelling occurs around the eyelid, it is referred to as Romaña’s sign (shown in many textbooks), but in reality, this finding only occurs in 1-2% of cases. In extreme situations, acute cardiac abnormalities such as atrio-ventricular block or myocarditis may occur. During this period, parasites are readily detectable in the blood via microscopy. In approximately 90% of individuals, the acute phase resolves spontaneously. It is important to remember, however, that many Chagas patients never exhibit acute symptomatology and therefore do not know that they have been infected.
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| Romaña's sign in acute Chagas diesease |
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| Trypanosoma cruzi parasites in the bloodstream during acute Chagas infection |
During the indeterminate phase, the patient is clinically asymptomatic, and parasites are not detectable in the blood. Chagas disease can be diagnosed, however, using immunological and molecular methods such as immunochromatography and ELISA (see below). Up to 70% of patients in the indeterminate phase have no further progresión of their disease and remain asymptomatic. However, some are vulnerable to sudden cardiac death due to conduction abnormalities, even without having been diagnosed with Chagas disease.
The chronic phase occurs about 10-30 years after inital infection and affects approximately 30% of Chagas patients in the indeterminate phase. The chronic phase implies organ damage, as the parasite gradually damages the nerve cells of the heart and/or intestines. The cardiac consequences range from arrhythmias to ventricular enlargement to frank heart failure. The gastrointestinal consequences include chronic constipation, megacolon, and megaesophagus due to inability to conduct parastalsis. Chagas disease is a leading cause of congestive heart failure in Latin America, and by the time patients reach this stage, there is very little recourse for them, as multiple medications, pacemakers, and heart transplants are extremely difficult to access due to financial constraints.
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| A ventricular aneurysm in the heart of a patient with Chagas |
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| Megacolon |
Transmission of Chagas Disease
Chagas disease transmission occurs primarily through vector-host interactions (i.e. humans getting bitten by the vinchuca). Other less common modes of transmission include blood transfusions and mother-child transmission. There have been rare reports of contaminated food leading to infection. Recent governmental efforts in several Latin-American countries have enhanced screening of the blood supply and deterred donations from infected patients, resulting in markedly reduced rates of infection from blood transfusion.
Diagnosing Chagas Disease
Traditionally, Chagas disease has been diagnosed using direct microscopy during acute infection. However, since Trypanasoma parasites are only visible in the blood during the acute phase, this is not a reliable method of diagnosis for patients in the indeterminate or chronic phase. Nowadays, the most commonly-used tests involve detection of antibodies against the Trypanosoma parasite. All Chagas patients, whether in the acute, indeterminate, or chronic phase, have detectable antibodies against T. Cruzi.
In Bolivia, as in many other Latin American countries, two principal tests are employed. The first is a rapid, immunochromatography-based test called a Stat-Pak (Chembio Diagnostic Systems, Medford, NY), which takes 10 minutes and only requires a drop of blood from a fingerprick. Even though the sensitivity ranges from 98.5-100%, a confirmatory test is necessary to discount false negatives. This second test, called an ELISA, requires drawing a tube of blood, sending it to the laboratory for analysis that often takes several days, and actually measures levels of the T. cruzi antibody in the blood. Once a patient tests positive with both the Stat-Pak and the ELISA, they are confirmed positive and therefore considered for treatment.
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| Chagas Stat-Pak |
Treating Chagas Disease
Before starting treatment, every newly-diagnosed patient should receive a 12-lead baseline electrocardiogram (EKG). In patients with cardiac or gastrointestinal symptoms or abnormal EKG, guidelines from the United States also recommend an echocardiogram, 24-hour holter monitor, and barium swallow (if gastrointestinal symptoms are present), but cost and resource scarcity make these studies prohibitive throughout most of rural Latin America. Patients who present with signs and symptoms of advanced heart disease are generally not offered treatment, since the Chagas parasite is thought to have already caused irreversible damage, and treatment will not improve any current symptomatology. (For more details, see "Evaluation and treatment of chagas disease in the United States: a systematic review".JAMA 298 (18): 2171–81)
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| EKG changes: The typical combination of Right bundle branch block and Left anterior fascicular block seen in Chagas disease (www.frca.co.uk) |
The two drugs currently available for Chagas treatment are Benznidazole and Nifurtimox. Interestingly, neither drug is on the list of essential medicines for most Latin American countries, indicating the general lack of funding, advocacy, and awareness of Chagas disease worldwide (see below for more details). Both drugs have shown up to 80% cure rates of acute Chagas, while documented cure in chronic patients is harder to achieve. The downside of these drugs is their side effect profile, which leads to non-compliance in a large number of patients, particularly adults. The treatment course also lasts for 6 weeks and requires weekly clinical monitoring for side-effects. Clinical trial dropout rates with both of these drugs have approached 20-30%. Accordingly, more effective Chagas drugs with fewer side effects are urgently needed, and research on that front has been slow and underfunded.
An important adjunct to medical treatment for Chagas is vector control. It makes little sense to treat a patient for Chagas disease, only to have her go back to her same house where infected vinchucas live. Accordingly, in many Latin American countries, it is a necessary criterion to spray the patient's house with insecticide once she is diagnosed, before starting treatment. Several vector control campaigns in Brazil, Venezuela, and Uruguay, for example, have demonstrated that multi-country pacts backed by legislation can dramatically reduce the incidence of Chagas disease and cross-border transmission.
Chagas: A Neglected Tropical Disease
For further general information about Chagas, go to
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| Benznidazole |
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| Nifirtamox |
An important adjunct to medical treatment for Chagas is vector control. It makes little sense to treat a patient for Chagas disease, only to have her go back to her same house where infected vinchucas live. Accordingly, in many Latin American countries, it is a necessary criterion to spray the patient's house with insecticide once she is diagnosed, before starting treatment. Several vector control campaigns in Brazil, Venezuela, and Uruguay, for example, have demonstrated that multi-country pacts backed by legislation can dramatically reduce the incidence of Chagas disease and cross-border transmission.
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The Vinchuca: a slippery feller |
Chagas: A Neglected Tropical Disease
For further general information about Chagas, go to
Chagas in Bolivia
Bolivia has the highest per capita prevalence of Chagas disease in the world, affecting approximately 20% of the population, or 2 million people. In certain rural villages, prevalence approaches 80%. Effective Chagas control in Bolivia has been stymied by lack of private and government resources for widespread screening, diagnosis, treatment, and vector control programs. Up until recently, the prevailing practice of the Bolivian medical establishment has been to only treat children in the acute phase of the disease. With recent literature suggesting that adults and chronic Chagas sufferers may also benefit from treatment with Benznidazole, however, the current of opinion is gradually shifting. (See Viotti R, Vigliano C, Lococo B, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med. 2006;144(10):724-734.)
As a result, the Bolivian government and Doctors Without Borders (Médicins sans Frontières, or MSF) have teamed up to roll out a comprehensive screening, diagnosis, and treatment program nationwide. The program is supposed to offer these services free of charge to patients, but the problem is that many gaps in services still exist in many areas outside the large cities. Ideally, the key steps to this project are:
As a result, the Bolivian government and Doctors Without Borders (Médicins sans Frontières, or MSF) have teamed up to roll out a comprehensive screening, diagnosis, and treatment program nationwide. The program is supposed to offer these services free of charge to patients, but the problem is that many gaps in services still exist in many areas outside the large cities. Ideally, the key steps to this project are:
1. Screening and Diagnosis: Screening in endemic areas is done using the rapid test (Stat-Pak). If the rapid test is positive, diagnosis is confirmed with an ELISA.
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| A nurse from Doctors Without Borders demonstrates proper technique for doing the rapid test. |
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| Only one drop of blood is needed to put on the Stat-Pak window. |
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| Negative result (L) and test in progress (R) |
3. Vector Control: While patients waits for their ELISA and/or EKG results to come back (which often takes weeks), they are encouraged to capture and bring in a vinchuca from their house. Staff from the ministry of health pick up these vinchucas from the clinics and test them for T. cruzi parasites. If the vinchuca is positive for T. cruzi, government workers come to the patient's house and fumigate it.
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| Vinchucas brought into the Clínica Villa Israel from the local school |
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| A government health worker fumigating in one of the villages |
4. Treatment: First-line treatment in Bolivia is with Benznidazole. A full treatment course lasts 6 weeks, and the patient must come back to a health center weekly to document compliance and monitor for side-effects.
In practice, there is difficulty completing many of these steps in a timely manner. Especially in rural villages, there are often not enough resources to provide screening kits to an entire community. Or, a patient may be diagnosed serologically, but they must go to the nearest city to receive an EKG and have it read--this delay creates a bottleneck in the system. Additionally, many patients opt not to begin treatment, or do not complete treatment, despite the free cost of medications. Our project aimed to address some of these glitches in the system and elucidate suggestions on how to improve overall Chagas care in Bolivia.
Our Chagas Project
In some parts of Bolivia, despite availability of treatment, fewer than 30 percent of seropositive patients return for follow-up evaluation and treatment. Consequently, very little is known about treatment adherence, post-treatment morbidity and mortality, and what factors affect treatment completion. Our project aimed to address two main questions:
1. Despite having free diagnosis and treatment available, why do so few patients end up completing treatment?
2. Is there a correlation between progression of Chagas symptoms and whether a patient completed treatment or not?
The project protocol was quite simple. Our target population was patients who had been diagnosed with Chagas disease through the government/MSF program, offered treatment, and were either lost to follow-up, did not complete treatment, or did complete a full treatment course. Our main strategies were to:
We decided to base our project in Cochabamba because Mano a Mano Bolivia (the NGO sponsoring us) is based there and recommended a number of their clinics in the area with whom we could collaborate to recruit patients. In order to perform EKGs on multiple patients in a resource-poor setting, we bought a portable EKG machine on eBay and brought it down to Bolivia with us. When we first approached a few of these Cochabamba clinics with our project proposal, the directors became very excited about our having an EKG machine and asked us if we would be willing to do baseline EKGs on several of their patients who had already received their diagnosis but not yet started treatment. Since these clinics were allowing us access to their patient records so that we could recruit them for our survey, we agreed to help them with their regular operations of the local Chagas program by doing EKGs for new patients.
Our Project Site
At Mano a Mano's recommendation, we decided to focus our clinical and project efforts at the Clínica Villa Israel, a small, primary care clinic located 30 minutes outside the center of Cochabamba.
This clinic was a good choice because the medical director, Dr. Hilda Ramírez, has a good relationship with Mano a Mano and is extremely dedicated to improving and expanding her clinic's Chagas diagnosis and treatment program. In collaboration with the Bolivian government and Doctors Without Borders, Clínica Villa Israel began a comprehensive screening, diganosis, and treatment program starting in June 2009. Consequently, there were over 100 clinic patients who had been offered treatment and were therefore eligible for our study.
During our first month in Bolivia (July-August 2010), we oriented ourselves to the clinic by seeing patients with the doctors and helping out with the Chagas screening program.
Our Chagas Project
In some parts of Bolivia, despite availability of treatment, fewer than 30 percent of seropositive patients return for follow-up evaluation and treatment. Consequently, very little is known about treatment adherence, post-treatment morbidity and mortality, and what factors affect treatment completion. Our project aimed to address two main questions:
1. Despite having free diagnosis and treatment available, why do so few patients end up completing treatment?
2. Is there a correlation between progression of Chagas symptoms and whether a patient completed treatment or not?
The project protocol was quite simple. Our target population was patients who had been diagnosed with Chagas disease through the government/MSF program, offered treatment, and were either lost to follow-up, did not complete treatment, or did complete a full treatment course. Our main strategies were to:
- Devise and administer a survey to these seropositive patients, many of whom had been lost to follow-up. The survey inquires about demographics, date of Chagas diagnosis, whether treatment was completed, disease symptoms, and factors affecting treatment course such as medication side-effects and cultural perceptions of disease.
- Offer a follow-up EKG to these patients, compare it to their baseline pre-treatment EKG to see if any cardiac changes were present, and determine if any correlation existed between new cardiac abnormalities and whether the patient completed treatment.
We decided to base our project in Cochabamba because Mano a Mano Bolivia (the NGO sponsoring us) is based there and recommended a number of their clinics in the area with whom we could collaborate to recruit patients. In order to perform EKGs on multiple patients in a resource-poor setting, we bought a portable EKG machine on eBay and brought it down to Bolivia with us. When we first approached a few of these Cochabamba clinics with our project proposal, the directors became very excited about our having an EKG machine and asked us if we would be willing to do baseline EKGs on several of their patients who had already received their diagnosis but not yet started treatment. Since these clinics were allowing us access to their patient records so that we could recruit them for our survey, we agreed to help them with their regular operations of the local Chagas program by doing EKGs for new patients.
Our Project Site
At Mano a Mano's recommendation, we decided to focus our clinical and project efforts at the Clínica Villa Israel, a small, primary care clinic located 30 minutes outside the center of Cochabamba.
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| Centro de Salud Villa Israel, our home base. Blanca, the dog, is our unofficial mascot. |
This clinic was a good choice because the medical director, Dr. Hilda Ramírez, has a good relationship with Mano a Mano and is extremely dedicated to improving and expanding her clinic's Chagas diagnosis and treatment program. In collaboration with the Bolivian government and Doctors Without Borders, Clínica Villa Israel began a comprehensive screening, diganosis, and treatment program starting in June 2009. Consequently, there were over 100 clinic patients who had been offered treatment and were therefore eligible for our study.
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| Me with Dr. Hilda Ramírez, medical director of Villa Israel Clinic |
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| Young patients waiting outside the clinic to be seen |
Villa Israel is a primary care clinic, but the majority of patients are young children and pregnant women, since the Bolivian government has established a "bonus" program though which mothers receive a small amount of money for every well child visit and prenatal care visit they attend. It's an effective way of promoting preventive care, but the result is that there are often lines out the door of the clinic every day, and many have to be turned away and be told to come back the following day.
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| Mothers and children in the waiting room usually wait for hours to be seen |
Villa Israel is also fortunate to have a comprehensive nutrition program, by which nutrition students from the local universities rotate through the clinic and give integrated services to all patients, including height/weight checks, nutrition talks, community outreach, and breastfeeding counseling. We became very good friends with the group of nutritionistas who were working in the clinic between August and October 2010. We cooked meals together and even went out to the discoteca on weekends!
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| Nutritionists Melissa, Marianela, and Silvia working on a presentation |
Before we started collecting data, we began helping out with the clinic's Chagas screening program in order to orient ourselves to daily operations. We would screen approximately 7 patients per day, and about 1 out of every 2-4 patients was positive.
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| The Chagas screening room |
Project Course thus far
During August and September, we had several meetings with all the local organizations involved with Chagas in Cochabamba--NGOs, government health officials, and clinic directors--to make sure that everyone was on board with our project and to see if they could lend us any advice. This whole process took forever because every agreement about proceedings requires a formal letter with the signatures of all parties involved, as well as their "official" stamps. In order to get the signature of each party, it's necessary to have a meeting with them, draw up a draft of the letter, review the letter draft with each party, and take the letter to each office to get their signatures and stamps. Mostly everything is done by hand here, so email and online recourses are not as common ways to circulate information. Initially, we had the support of the organizations we had met with, and some of them, including Doctors Without Borders, were wonderful about giving us a background of their current Chagas work and what the proper guidelines were.
Sara built an extensive database of Chagas positive patients at the clinic by reviewing charts and identifying which ones were eligible for the study. Afterwards, the hard part was contacting patients lost to follow-up, because only a fraction of the clinic patients had phone numbers, and of those phone numbers, some of them had been since disconnected. Nevertheless, we were able to recruit some of them back to the clinic, and we started enrolling our first patients in the study in late September.
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International health development work: the ultimate challenge in diplomacy and learning how to play well together. (L to R: Doctors without Borders, Me, Andrew, Bolivian Ministry of Health) |
Unfortunately, after a few weeks, one of the local NGOs became suspicious of our operations and advised us to back off the study, because they felt uncomfortable with some of the elements of our protocol. They said we had not been transparent about all the steps in the protocol, and after reviewing the protocol again, they said that they did not advise carrying forward with one of its key steps. We found this accusation strange, since we had distributed printed copies of the protocol to all the local organizations who had signed the letters, as well as emailed it out to organization directors.
Regardless, they formally broke all ties with us and advised the government that our work was in no way related to theirs. After this shocking development, we decided to go back to the government health officials and confirm that we still had their permission to proceed with the study. Luckily, they were still on board with the study and were able to sign yet another letter saying as such.
These events happened in mid-October. Afterwards, we decided to switch gears a bit and explore doing the project in a part of the country where there wasn’t so much red tape. Accordingly, we did an EKG campaign in Potolo (Chuisaqua state) at the end of October and are still considering following up there with our survey (please see below).
In the meantime, Andrew and I took a hiatus from the project during November, when he and I went back to the States. When we come back in December, we will have to decide where to focus our efforts—whether in Cochabamba or in Chuquisaca.
Sara and Chris were with us for only 2 months, but whatever progress we have made on the project so far would not have been possible without their contributions. They were singlehandedly responsible for developing the Villa Israel Chagas screening program, finding numerous patients who had been lost to follow-up, and developing an excellent patient database. Additionally, they helped a lot with EKGs, finetuning our survey, and general advice about project operations. We are extremely grateful for their help and wish them the best on their travels for the rest of the year.
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Andrew, Sara, Ubaldina and I cruise to the clinic in a borrowed Volkswagen bug (They call them "Petas" in Bolivia--meaning turtle) |
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Ubaldina, Chris, Andrew, and I take the Peta for a spin |
