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Against ascites (abdominal dropsy)

A team from the state of Minas Gerais State presents new prospects for a vaccine against schistosomiasis

eduardo cesarIn Brazil, elevated levels of schistosomiasis: inattentiveness towards water contaminationeduardo cesar

In 1986, on returning to Brazil with his doctorate degree from John Hopkins University in the United States, Rodrigo Correa-Oliveira could have preferred to live tucked away in one of the Oswaldo Cruz Foundation (Fiocruz) laboratories in Belo Horizonte, but no. The biologist from the Minas Gerais State, who today could be on the trail of a vaccine against a disease that afflicts the developing world, then took out his high heeled boots and hat from the bottom of his wardrobe, caught a bus and two days later got off at the Jequitinhonha Valley, one of the poorest regions in Minas Gerais.

During weeks, disposed to better understand the mechanisms of the schistosomiasis transmission, he traveled along the dusty roads of Padre Paraíso, of Itaobim and of other municipalities that hardly appear on the map. He spoke with the inhabitants of these rural communities and turned over, using a borrowed spade, the vegetation at the edges of the streams and lakes in search of periwinkles, the transmitters of the worm named Schistosoma mansoni, which causes the illness also known as abdominal dropsy because of an uncommon swelling of the liver and spleen. Common in the north of Minas Gerais, schistossomosis assaults approximately 12 million people in Brazil – in the whole world around 200 million people suffer from this illness, typical of less developed countries.

Twenty years later, still with the habit of traveling at least once per month to the Jequitinhonha Valley or to the Mucuri Valley, Oliveira and researchers from Australia and the United States have demonstrated that two proteins on the surface of Schistosoma mansoni bring the defense mechanisms of the organism of mice into action against the worm. If in tests with human beings they also bring positive results, these proteins – called transpanins – could become candidates for a vaccine against schistosomiasis, to be adopted in conjunction with other measures to combat the illness, mainly the widening of sewage drains and the treatment of water, since the worm of up to 12 millimeters in length and 0.4 millimeters in diameter, is spread by way of contaminated human feces.

According to Oliveira, a vaccine is justified because the illness had already spread over vast areas of the country, making difficult a campaign for the elimination of these transmitters, the periwinkles of the genre Biomphalaria. As well as this, schistosomiasis is beginning to demonstrate resistance to the two drugs most widely used, oxamniquine and praziquantel. Another problem: “The treatment only by itself”, he stated, “is not sufficient to avoid re-infection, mainly in children”. With distinct occurrences, groups from the University of São Paulo (USP) and the Butantan Institute are working on other alternatives.

Natural resistance
This new pathway towards a vaccine came about from a hypothesis formulated by Oliveira in 1985 after having read a study about people whose organism presented natural defense mechanisms against filariasis, another illness typical of poor countries that makes the legs swell enormously. As both elephantitis and schistosomiasis are caused by worms of the helminth group, he imagined that the human body could put into action natural forms of also escaping from schistosomiasis. The biologist who began to study immunology in 1978, still in his undergraduate days, then set out for the confines of Minas Gerais in search of people who has entered into contact with this worm but had not shown any symptoms of the illness. And he found them.

In the laboratory, after having analyzed the types and quantities of antibodies in these people’s blood, Oliveira discovered that the answers that they had presented were very different from those registered after treatment with the medicines that kill of the worms. As he described in 1989 in the magazine Transactions of the Royal Society of Tropical Medicine and Hygiene, the organism of the people resistant to schistosomiasis combat the worm by way of an intense – and almost exclusive – production of antibodies, brought into action by communication molecules such as immunoglobulin E and gamma interferon.

It was also in 1989 that Oliveira found one of the proteins capable of bringing into action the phenomenal production of antibodies in people who live among contaminated periwinkles. They also contaminated themselves, but without knowing how they managed to rid themselves of the worm. But this protein, named paramyosin, was not very friendly in the laboratory, and the researchers did not manage to advance. Years passed before the biologist from Minas Gerais proposed to Alex Loukas, from the Queensland Institute of Medical Research in Australia, that they work in conjunction to find out if other proteins, the transpanins, could intensify the production of antibodies. This time things worked out. According to the study published on the 18th of June in Nature Medicine, which also had the participation of Jeffrey Bethony, from George Washington University in the United States, in individuals naturally resistant to transpanin 2 (TSP-2) it is easily recognized by immunoglobulins. Nothing happens, however, with people in whom the infestation progresses. In mice, the TSP-2 set off a series of responses that led to a reduction of up to 64% in the quantity of worms; with another transpanin, namely TSP-1, the quantity of eggs of Schistosoma fell by half. Another exciting piece of information is that the two transpanins are recombinants: they can be produced in elevated quantities by way of bacteria and afterwards purified.

Against the hookworm
Oliveira and all of the team with whom he worked know that this is only the beginning. As yet they need to show, by way of tests that must be done during this year directly on the blood of human beings, that these results can be repeated – or even improved – and that it is worthwhile to invest money and time in this line of research. After comes the technology stage, beginning with the so called scaling, by way of which one attempts to amplify in hundreds of times the production of the potential vaccine. However, this is not a new road for Oliveira, who gained experience dedicating himself to the development of another vaccine – against ancylostoma or hookworm, another disease found in countries where people still live who walk barefoot in dirty environments.

Once the laboratory stage has been won, the team from Minas Gerais Fiocruz, currently with groups from the Sabin Vaccine Institute, of George Washington University and the Butantan Institute, are working in the preparation of experimental lots of a protein that will then be tested on human beings with the proposition of eliminating the hookworms Necator americanus and Ancylostoma duodenale. These parasites cause profound anemia in around 800 million people in the world by damaging the intestine wall and bringing about the loss of up to a cup of blood per day.