Disease of Chagas

The American trypanosomiasis (Brazilian) or disease of Chagas is a form of Trypanosomiase (like the Maladie of the sleep), a parasitic disease which prevails in the tropical areas of central South America and . It is caused by Trypanosoma cruzi , a Trypanosome which is transmitted by S hematophagi of the kinds Triatoma and Rhodnius (family of the réduvidés , the such Vinchuca ( Triatoma infestans , Triatoma protracta and Rhodnius prolixus ). According to WHO close to 13 000 people die of the badly of Chagas and 300 000 new cases are declared each year. It bears the name of the Brazilian doctor, Carlos Chagas which for the first time in 1909 described the disease.

History

The disease was baptized name of the Médecin Brésil IEN specialist in the infectious illness Carlos Chagas, which described it for the first time in 1909. '' But, the disease was not regarded as an main issue of Public health at the man before the years 1960 (the manifestations of the disease of Chagas in Brazil in years 1920 were largely ignored).

He discovered that the intestines of the Triatomae lodged a Protozoaire whipped, a new species of the kind Trypanosoma and managed to prove in experiments that he could be transmitted to the monkeys marmouset S which had been piqués by the infected insect.

Chagas called the parasite Pathogène which causes the disease Trypanosoma cruzi , at the same time to honor Oswaldo Cruz, the remarkable doctor and Brazilian epidemiologist which had fought successfully epidemic S of Yellow fever, of Variole, and Bubonic plague with Rio de Janeiro and in other cities at the beginning of the 20th century. The work of Chagas is single in the Histoire of medicine because he was the only researcher until now describing completely a news Infectious illness: its disease-causing agent, its vector, its host, his demonstrations clinical and its epidemiology. Nevertheless, he however believed wrongly until 1925, that the independent source of infection was the insect bite - and not its dejections - as had proposed it his/her colleague Emile Brumpt in 1915 and like had confirmed it Silveira Dias in 1932, Cardoso in 1938 and Brumpt itself in 1939. Chagas was also the first to discover and illustrate the parasite of the fungic kind Pneumocystis , (which will be known good to later be the cause of the Pneumocystose of disaster reputation at the victims of the AIDS).

Epidemiology and geographical distribution

The disease of Chagas currently assigns 16 to 18 million people, with some 100 million others (25% of the Latin-American population) potentially exposed to the risk to contract the disease,

The chronic disease of Chagas remains an important health issue in many countries of Latin America, in spite of the effectiveness of measurements of hygiene and prevention, such as the elimination of the insects vectors of the transmission, which reduced to zero the number of new infections in at least two countries of the area. With the increase in the shifts in population, the transmission risk by blood transfusion however became more real in the United States. Moreover, T.cruzi already proved to be able to infect the wild Opossum and the Raccoon until far in north in a State like the North Carolina.

The disease is present in almost all the America S, of the south of the the United States in the south of the Argentine, most of the time in poor rural areas, of Central America and South America.

The disease meets almost exclusively in the rural areas, where Triatominae can multiply and find their food on a natural basin of T.cruzi (most widespread being the Opossum and the Tatou). According to the local interactions between the vectors and their hosts, the other human ones infected, as well as the pets like the Cat S, the Dog S, the guinea-pig S and the wild animals like the Rodent S, the Monkey S, the squirrel S (Spermophilus beecheyi) and much of others could also be important tanks of parasite. Although Triatominae are nourished on the birds, those seem to be immunized against the infection and thus are not regarded as a tank of T. cruzi ; but of the suspicions remain on their role like food resource for the vectors close to the human dwellings.

The insects of the triatomine kind are known in various countries under popular names of vinchuca , of barbeiro (the barber), of chipo and other names, are usually hidden during the day in the cracks and the holes in the walls and the roofs of the badly built houses. More rarely, the better built houses can lodge the Insecte vector, because of the use of materials of bad quality to make roofs, like the Bambou and the Chaume. A Mosquito net, rolled under the mattress, will ensure a protection in these situations, when the adult insect can come from the top to the bottom, but a larva of one of the five stages nymphales (the Instars) is able to crawl of the floor upwards.

Even when the colonies of insects are éradiquées of a surrounding house and shelters for the pets, they can return (for example, while flying) starting from the plants or from the animals which belong to the ancient cycle of natural woodland infection. This can occur particularly in the zones of open savanna inserted between thickets of trees and human dwellings.

Dense vegetation, as in a Tropical forest, and the urban habitats, does not offer ideal conditions for the establishment of the cycle of human transmission. However, in the areas where the forest habitat and its fauna are nibbled by the economic exploitation and the extension of the human habitat, as in the lately déforestées zones, piassaba palm, ( Leopoldinia piassaba ) zones the cultivated and certain parts of the Amazonia, the disease can reappear, when the insects seek a new prey.

Clinical demonstrations

The human disease develops in two phases: the acute phase little time after the Infection, and the chronic phase which can extend over one 10 years duration.

In the acute phase, an isolated cutaneous nodule called a chagoma can appear at the point of inoculation. When this point of puncture is conjunctival and mucous, the patient can develop a unilateral Conjonctivite and a edema périorbitaire, as well as a Lymphadénite préauriculaire. This constellation of symptoms is indicated by the term of sign of Romaña . The acute phase is usually Asymptomatique, but can present demonstrations to type of Fièvre, Anorexie, Lymphadénopathie, light Hépatosplénomégalie, and Myocardite. Certain acute cases (10 to 20%) attenuate into 2 to 3 months to make place with an asymptomatic chronic phase and to only reappear after several years.

The symptomatic chronic phase can not occur before years or even decades after the initial infection. The disease affects the Nervous system, the digestive Système and the Cœur. The chronic infection involves various central nervous system disorders, going until the Démence, an attack of the cardiac muscle (the Cardiomyopathie which is the most serious complication), and sometimes a dilation of the digestive Tract (Mégacolon and Mégaoesophage), as well as a weight loss. Disorders of swallowing can be in the forefront of the digestive symptoms and can lead to a Malnutrition. After several years of asymptomatic phase, 27% of the infected subjects present cardiac lesions, 6% of the digestive disorders, and 3% a peripheral nervous attack. In the absence of treatment, the disease of Chagas can prove mortal, in the majority of the cases because of an associated Cardiomyopathie.

Parasitic cycle

Additional transmission systems

The researchers suspected since 1991 that the transmission of the trypanosome was possible by oral way, because of a certain number of microphone-epidemics limited to periods and particular places (such as a farm or a family housing), in particular in not-endemic sectors such as the Amazonia (17 episodes of this type were recorded between 1968 and 1997). In 1991, farm laborers of the State de Paraíba, in Brazil, were apparently infected by the consumption of food contaminated by dejections of Opossum; and in 1997 with Macapá, in the State d' Amapá, 17 members of two families were probably infected by drinking fruit juice of palm tree assai contaminated by insects vectors crushed of triatomine type.

To the beginning of the year 2005, a new epidemic with 27 cases was announced in the Amapá.

In March 2005, a new spectacular demonstration was recorded in the State de Santa Catarina, in Brazil, which seemed to confirm this alternate mechanism of transmission. Several people of Santa Catarina who had introduced juice of Canne to sugar (Garapa, in Portuguese) into a kiosk at the edge of the road contracted the disease of Chagas.

In March 30th, 2005, 49 cases had been confirmed in Santa Catarina, including 6 death.

The supposed mechanism, until now, is that insects carrying the trypanosome were crushed in the raw material. The services of hygiene of Santa Catarina estimated that 60 000 people could have been in contact with contaminated food with Santa Catarina and invited all the people concerned to subject itself to blood tests. They prohibited the sale of the cane sugar juice in the State until the risk either circumscribed.

The unusual gravity of this epidemic was allotted to a hypothetical particularly high parasitic load which would have been at the origin of this infection transmitted by oral way. The Brazilian researchers of Institut Oswaldo Cruz, with Rio de Janeiro, were able to infect mice by digestive tract with preparations infected by the trypanosome.

Diagnosis of laboratory

The description of the causal agent is the procedure of diagnosis used in the acute phase of the disease of Chagas. It almost always gives positive tests, and can be realized by:

Examination with the Microscope:

a) Of Blood fresh taken on anticoagulant or globular base, for the mobile parasites; b) A spreading out of blood contaminated on blade fixed at the dye of Giemsa, for the visualization of the parasite; it can be confused with Trypanosoma rangeli , 50% longer which is not regarded as pathogenic for the man.

Insulation of the agent by:

) Inoculation with the mouse A;

B) Culture on special medium (for example, NNN, READS) etc.)

c) Xenodiagnosis, a test during which the Réduve S, not infected insects are nourished by the blood of the patient, and the contents of their intestine are tested for a search for parasites during the 4 weeks which follow.

Tests varied from immunological diagnosis; (while also trying to distinguish the stocks from (Zymodeme S) from the T.cruzi which has a different pathogenicity).

indirect Fixing of the complement
Hémagglutination.
Analysis in indirect immunofluoresence]]
Analysis in Radioimmunology
Analysis ELISA (titration immunoenzymatic using an absorptive antigen).

Diagnosis by techniques of molecular biology.

PCR, chain reaction of polymerase, the most promising technique

Forecast

An index for the evaluation of the forecast of the patients who have the disease of Chagas was published in the edition of August 24th, 2006 of the New England Journal off Medicine .

Based on the study of more than 500 patients, this index includes aspects clinical, radiographic, electrocardiographic, echocardiographic and results of recording Holter and makes it possible to evaluate the forecast of survival at ten years of the patients.

Treatment

The drugs used to treat the disease of Chagas are usually effective only if they are managed during the acute phase of the infection. The molecules of choice are the azole or the derivatives nitrated like the Benznidazole. or the Nifurtimox (a new therapeutic protocol is in the course of investigation by the pharmacological service of CDC), but of resistances to these molecules were already brought back.

Moreover, these substances are very toxic and have many side effects, and cannot be managed without medical supervision. The agent antifongic named Amphotéricine B was proposed like treatment of second intention, but the cost and the relatively high toxicity of this molecule limited its use. Moreover, a study on the administration prolonged of drugs during ten years in Brazil indicated that current chemotherapy did not remove the parasitemy completely.

Thus, the decision to manage a therapy Antiparasitaire should be individualized after consultation with a specialist.

In the chronic phase, the purpose of the treatment is to control the clinical demonstrations of the disease, for example, drugs to stimulate the heart, to avoid the heart failure and the disorders of the rate/rhythm; surgical treatment for the mégacôlon, etc, but the disease it even is not curable in this phase. The chronic cardiac demonstrations caused by the disease of Chagas are now a current indication of heart Transplant. Until recently, however, the disease of Chagas was regarded as a contrindication with transplantation, since the cardiac lesions could repeat when the parasite would seize to develop the opportunity provided by the immunosuppressor treatment which follows surgical operation. The research which changed the indication of transplantation for the patients reached of the disease of Chagas was undertaken by the team of Dr. Adib Jatene to the institute of the heart of the university of São Paulo, with São Paulo, Brazil.

Research showed that the rates of survival among patients reached of disease of Chagas could be appreciably improved by using weaker amounts of immunosuppressor Cyclosporine. Recently, the transplantation of osseous Marrow and the injection in the cardiac muscle of original cells was effective to clearly reduce the risks of cardiac arrest among patients reached of Chagas.

Patients also drew from the benefit of the strict prevention of the réinfection, although the reason of this phenomenon is not yet clearly elucidated.

Some examples of the fight for therapeutic projections:

the use of the inhibiters of the Oxidosqualene cyclase and the inhibiters of the Cystéine protease proved to be effective to treat the experimental infections in the animals.

the Dermaseptine S coming from a frog of the species Phyllomedusa oreades and P. distincta . Activity Anti Trypanosoma cruzi without Cytotoxicité for the cells of mammals.

Synthesis of inhibiters of the enzymes implied in the metabolism of the Trypanothione which is specific to the group of the whipped parasites.

the dehydroleucodine sesquiterpene lactone (DHL) affects the growth of the cultures of Epimastigote S of Trypanosoma cruzi .

the Génome of Trypanosoma cruzi was sequence.

Proteins which are produced by the disease but not by the human ones were identified like possible targets for drugs against the disease.

Prevention

A sufficiently effective Vaccin was developed with Ribeirão Preto in the Seventies, by using cellular and under-cellular fractions parasite, but it was impossible to market for economic reasons. More recently, of the potential vaccines by DNA recombining for the immunothérapie disease of Chagas acute and chronic were studied by several groups of research.

The prevention is based on the fight against the vector ( Triatoma ) by using aerosols and paintings containing of the Insecticide S (Pyrèthrinoïde S of synthesis), and by improving housing and the sanitary arrangements in the rural areas. For the inhabitants of the cities, it can be dangerous to spend the holidays and to camp in the open air, in the arid zones or to sleep in hotels or houses out of cob in zones of endémie, a Moustiquaire is recommended. If the traveller for travelling in a zone at the risk it should be able to obtain information on the zones of endémie of the disease of Chagas in bulletins of information for the travellers, such as CDC.

In the majority of the countries where the disease of Chagas is endemic, blood testings are already obligatory for the blood donors, since the transfusion can be an important way of transmission.

In the past, the blood of the donors was mixed with 0.25 g/l Violet of gentian to highlight the parasites.

With all these measurements, some results were reached in the combat against the disease of Chagas in Latin America: a reduction of 72% of the incidence of the human infection in the children and of young adults of the countries of the initiative of the southernmost cone, and at least two countries (the Uruguay, in 1997, and the Chile, in 1999), were declared free from any transmission by a vector and transfusion. In Brazil, where most of the population exposed to the risk saw, 10 states out of the 12 at the endemic stage were also declared free of the disease.

Some benchmarks for the control of the vector:

a trap with yeast was tested to supervise the infestations by certain species of insects: “Effectiveness of the traps with yeast with Triatoma sordida , Triatoma brasiliensis , Triatoma pseudomaculata , and Panstrongylus megistus in tests laboratory. "

Of the promising results was obtained with the treatment of the habitats of the vector with the mushroom Beauveria bassiana, (which is also in the course of evaluation for the prevention of the Malaria): “Activity of a preparation of oil of Beauveria bassiana against the Triatoma sordida in peridomestic zones in the center of Brazil. ”

Targeting of the Symbion of the Triatominae.