Argentine laboratory tracks a killer

An inch-long bug is laid out on Mariano Levin’s desk at the Institute for Research in Genetic Engineering and Molecular Biology (INGEBI) in Buenos Aires, Argentina. Called the vinchuca , “kissing bug” or “assassin bug,” Triatoma infestans is a forest-dwelling insect that invades thatched roofs and cracks in mud walls of poor rural homes in northern Argentina and other parts of Latin America. It drops down on its victims, often at night, and infects them with a parasite, Trypanosoma cruzi, that causes Chagas disease, a potentially crippling and sometimes deadly affliction.

Levin explains how the parasite, a protozoan, only remains in the victim’s bloodstream for two months, during which “acute phase” it causes a fever. Then it hides in the tissue, where it may remain for 10 to 20 years without producing any symptoms. Eventually, though, the parasite may cause “bundle-branch block,” or damage to a branch of the heart’s bundle of conducting fibers that impedes the passage of electric impulses, leading to heart failure, as well as damage to other internal organs.

Genome sequencing. Scientists do not know how Trypanosoma cruzi causes the damage, but Levin is hot on the trail. His team, together with an international consortium of researchers, has already produced a draft of the parasite’s genome sequencing, which could lead to the development of better treatments. The team uses sophisticated equipment supplied by the Center for Applied Genomics at the University of Buenos Aires (CeGA, the first gene sequencing center of an Argentine university). The equipment was paid for under a technology modernization program that received support from the Inter-American Development Bank. The research project also includes studies on immunology, patient care and parasite control.

INGEBI was established in 1980 by Argentina’s National Council for Scientific and Technical Research (CONICET), and has worked closely with the University of Buenos Aires, where several of its researchers teach. INGEBI also promotes cooperation with the business community to transfer the results of its research and development. Several INGEBI teams are currently conducting research on Chagas disease that was initially financed by CONICET and since 1986 has been supported by the Pan American Health Organization (PAHO), the regional branch of the World Health Organization (WHO). Levin’s team receives additional support from the Howard Hughes Medical Institute in Chevy Chase, Maryland.

Networking for results. Levin’s Molecular Biology Laboratory for Chagas Disease has been expanding, so space is at a premium: the hallways are lined with refrigerators and other equipment, and a few visitors can barely squeeze into Levin’s office. He explains how, because the parasite cannot be detected in the bloodstream just two months after infection, doctors must test for antibodies instead to diagnose Chagas disease. The Chagas laboratory produces “recombinant antigens,” parasite proteins that make very good diagnostic reagents for Chagas.

Working with a network of research centers in Latin America that sent the INGEBI lab their diagnostic proteins, the group found a mix of recombinants to get the best reagent. Levin described the network cooperation as “very productive.” A pharmaceutical company, Chembio of the United States, which manufactures an HIV/AIDS diagnostic kit, bought the mix and produced a quick diagnosis kit called “Chagas STAT-PAK.”

The new kit gives a diagnosis in just 10 seconds, instead of several hours or even days, as was previously the case. The Chagas Stat-Pak is now tested and used by several government agencies and nongovernmental organizations in several countries of Latin America, currently in Honduras, Bolivia and the Amazon region (French Guyana), to determine whether Chagas is endemic in an area. The kit has been approved in several countries.

The Chagas laboratory has also partnered with researchers from other continents. It was the first lab selected by WHO for a South-South collaboration program, under which Kenyan researcher Benson Nyambega has joined the Buenos Aires team. He specializes in a related parasite, Trypanosoma brucei, which causes sleeping sickness, an African disease transmitted by the tsetse fly. On this day, Nyambega is busy filling test tubes with T. brucei genes, synthesizing proteins for diagnosis.

Nearby, researcher Vivian Labovsky is preparing an experiment that she will conduct where special equipment is used and precautions taken to avoid contamination. This line of research is exploring the parasite’s effects on human heart cells, with a view to eventually developing applications. Other research on antibody sequencing will help determine whether the antibody “cross reacts” with heart tissue to cause heart problems.

Treatment. Not only is Chagas disease difficult to diagnose, there is no cure and no vaccine or preventive medicine. Adults can be treated with a drug called benznidazole, which will reduce the likelihood of the victim developing heart disease. But the drug may produce allergic reactions, such as an intolerance to heat in the skin. These can be alleviated by following a low-fat diet and eliminating alcohol, because of the way the liver processes the drug.

In children, however, Chagas can be cured with benznidazole treatment if it is administered during the acute phase. The vinchuca actually transmits the disease through its feces, which enter the victim’s bloodstream through scratching. When a child is bitten on the face and scratches, it causes a distinctive swelling of the eye called “Romaña’s sign,” signaling acute infection.

INGEBI, with additional support from a private foundation, Fundación Bunge y Born, and Caritas (a nongovernmental organization), recently finished a project in Santiago del Estero, an area with a high Chagas infection rate. Following WHO recommendations, adults were treated with benznidazole in order to stop progression of the disease, kill the parasite and decrease the parasite load in infected, asymptomatic patients. Insect removal is another important course of action, the focus of another ongoing project in Añatuya.

Chagas and poverty. According to the World Health Organization, Chagas disease, which exists only in the Western Hemisphere, affects 16–18 million people from Mexico to the south of Argentina. After several years of an asymptomatic period, 27 percent of those infected develop cardiac symptoms, which may lead to sudden death, 6 percent develop digestive damage and 3 percent suffer damage to their peripheral nervous system.

Named after Carlos Chagas, a Brazilian physician who discovered the parasite and its vector the vinchuca in 1909, Chagas disease is spread mainly through poverty. The poor are most likely to live in homes with thatched roofs in rural areas and are less likely to be aware of the association between the vinchuca and the disease.

Although transmission is mainly by the vinchuca , it can also be congenital, when an infected mother passes the parasite to her baby, or transfusional, when a patient receives infected blood through a transfusion. T. cruzi-infected blood in blood banks in selected cities in the region varies from 3 percent to 53 percent, a higher prevalence than that of HIV infection and Hepatitis B and C, according to WHO. Chagas has also become an immigration issue in the United States and Europe precisely because of infected blood donors, as well as organ donors and parasites in wild animals.

According to the UNDP Human Development Report, the economic loss for the region due to early mortality and disability by this disease in economically most productive young adults currently amounts to more than US$8 billion, which is equivalent to 2.5 percent of the external debt of the whole region in 1995.

Levin is hopeful that his team’s current research on T. cruzi genome sequencing could lead to better treatment and that the Chagas antibody sequencing project may illuminate how Chagas disease causes heart disease. His laboratory is addressing one of the “neglected diseases” PAHO describes as “stigmatizing diseases of poverty that can only be tackled by leadership and a concerted political and economic effort.”