Although there are millions of people with Chagas, a disease that kills over 12,000 people a year, it has remained until now, a rather neglected tropical disease little heard of outside Latin America. However, the tide could be about to turn, because cases are growing in the US, Europe, Japan, and other wealthy regions, drawing attention to the disease as a potential growing market for private investment in new drug development.
According to an article published in Science yesterday, 19 August, cases of the disease are rising in other parts of the world, not because the insects carrying the parasite are spreading, but because large numbers of people who are already infected, are migrating from Latin America.
Up to 25% of people in Latin America may be infected with Trypanosoma cruzi, the parasite that causes Chagas disease. It is related to the trypanosome that causes sleeping sickness in Africa.
The parasite spreads by the bite of an insect called the reduvid bug or triatomines, also known as the kissing bug.
When the bug sucks the blood of a carrier, it ingests the parasite which spreads to other victims through feces that the bug deposits in the open wound it leaves on the skin. It is called the kissing bug because it feeds on the face of its sleeping victim.
Victims then rub the feces into the open wound, or their eyes, or their mouth, and this is how the parasite enters the bloodstream. It can also be transmitted via blood transfusion, or across the placenta during pregnancy, and less commonly, through organ transplant or contaminated food.
Chagas is considered a disease of poverty because the bugs live in cracks in the walls and roofs of mud, adobe and straw houses, typically found in urban slums in Latin America.
It can remain dormant in the bloodstream for years, emerging much later. Millions of people who contracted the disease decades ago still don’t know they have it because diagnosis is complicated: it requires several blood tests, and often the early stages present no symptoms. Unfortunately, once the chronic form sets in, treatment with current drugs is no longer effective.
There is no vaccine against Chagas, and a person can become infected again after treatment. About 20 – 30% of those infected develop the chronic form of the disease, up to 20 years afterwards. By this time, they could have irreversible damage to the heart, esophagus and colon. Heart failure is not uncommon once the disease progresses to this stage.
CheckOrphan, a non-profit organization based in Basel, Switzerland and Santa Cruz, California that is dedicated to rare, orphan and neglected diseases, estimates there are now around 300,000 people living in the US who are either sick with Chagas or carry the dormant parasite. Often, the first they know of it is when they donate blood, and the screening tests shows positive for Trypanosoma cruzi.
According to Doctors Without Borders/Médecins Sans Frontières (MSF), there are only two drugs available to treat Chagas: nifurtimox, and benznidazol, and there are serious problems with getting them to the people who need them. For instance in the case of benznidazol, only 1 lab in Brazil makes it, yet it is urgently needed in 21 Latin American countries. In the case of nifurtimox, the problem is cost; it is commercially available for 48 US dollars, per course of treatment, or about the same as what a Bolivian miner earns in a month.
But, even if access improves, these drugs are not ideal, because cure rates among chronic cases remains under 50%. More research and development is desperately needed, but so far this has not been forthcoming, because, according to MSF, the market for Chagas patients has been too small to motivate private sector investment.
However, as more and more cases emerge in wealthier countries, it appears the tide could be turning, as Mitch Leslie writes in another article in the same issue of Science, “… after years of stagnation, research into new treatments for Chagas disease has picked up”.
The US Food and Drug Administration (FDA), is about to initiate a phase I trial to test the safety of a K777, a protease inhibitor, as a potential treatment for Chagas disease. Also, two other drugs, both converted from current antifungal agents, are about to start phase II trials to find out if they eliminate the parasite in patients with the chronic form of Chagas disease.
Other activity is also under way, in anticipation of more private investment and interest. Researchers are starting to scour chemical libraries and molecular classes to look for potential drug candidates to fight a disease that kills more people in South America than malaria.
Written by Catharine Paddock PhD