What is Chagas disease? 

Chagas is a neglected, life-threatening disease that affects 6 to 7 million people, primarily in Latin America and is spreading to other regions because of population movements. It is caused by a parasite called Trypanosoma cruzi, which is transmitted to humans by the bites of insects called ‘kissing bugs.’ Transmission from mother to child and through contaminated food and drinks is also possible. 

Chagas disease often remains asymptomatic but will provoke severe complications in approximately 30% of infected people. Symptoms include damage to organs such as the gastrointestinal tract and the heart, with heart damage potentially leading to sudden death. As many people are not even aware they are infected until it is too late, the disease is sometimes called ‘the silent killer.’  

Despite the high burden, existing treatments for Chagas disease are far from optimal. They were discovered more than 50 years ago and can cause severe side effects. They also have to be administered for two to three months, making it difficult for patients to adhere to their treatment. Yet, making progress in finding better cures has been extremely difficult. 

The challenge with Chagas ‘biomarkers’  

Biomarkers are body characteristics — such as temperature, blood pressure, or the presence of antibodies in the blood — that can be measured to assess a medical condition. They can also measure how well the body responds to a treatment, for example, whether a medicine has eliminated parasites or viruses. 

Existing tools used to measure Chagas biomarkers and assess treatment efficacy have major flaws that keep researchers from determining whether a treatment is really working. One of the primary methods measures ‘seroreversion’. This involves tracking the disappearance of antibodies in the patient’s blood that are produced by the immune system in reaction to the pathogen of interest (in this case, Trypanosoma cruzi). 

When a treatment works, the body stops producing antibodies, making seroreversion a reliable tool for assessing drug efficacy. However, with Chagas disease, it can take years — even decades — to measure a decline in antibodies in adults, even after all Trypanosoma cruzi parasites are eliminated from the body (which clinicians refer to as ‘parasitological cure’). 

‘That means we cannot run a clinical trial using seroreversion alone to measure treatment outcomes. We would have to follow patients for ten years or more, which is not compatible with drug development timelines and costs. We don't have that time when we develop a new medicine,’ says Ivan Scandale, Discovery Leader at DNDi. 

Another commonly used method involves directly measuring the presence of the parasite’s DNA in the blood using polymerase chain reaction (PCR). However, Trypanosoma cruzi primarily resides in tissues, with very few parasites circulating in the bloodstream. As a result, the PCR method might not provide an accurate picture of the infection. For that reason, it is not accepted by regulatory authorities to register a drug for Chagas disease.