Chagas disease, caused by the mastigophoran protozoon Trypanosma cruzi, is endemic in Central and South Americas where it affects 10 to 12 million people and kills more than 15.000 patients each twelvemonth. Besides, between 60 and 80 million persons remain at hazard of T. cruzi transmittal in endemic states ( OPS. 2006 ) . Furthermore, there are several hundred 1000 people infected with T. cruzi in other parts of the universe due to migration of Latin Americans towards non-endemic states, largely in the USA, Canada, Australia, Japan and Europe. The parasite is transmitted to worlds by blood-sucking triatomine bugs ( Triatoma, Reduvidae, Hemiptera ) , by blood or organ transfusion, vertically ( in most of the instances congenitally ) from the female parent to the foetus and, less frequently, orally by nutrient taint with unrecorded parasites. The one-year incidence rate of infection in the endemic zone has been estimated to be 0,008 instances out of 100.000 dwellers by the Pan American Health Organization ( PAHO ) , with 41.200 instances of vectorial transmittal and 14.385 instances of inborn transmittal annually ( OPS. 2006, Pinto Dias et Al. 2010 )

Developmental rhythm and parasitological signifier

T. cruzi is a mastigophoran of the order Kinetoplastidae, household Trypanosomatidae, characterized by the presence of one scourge and a individual chondriosome which contains a specialised DNA-containing cell organ named kinetoplast. During its dixene rhythm, the parasite undergoes four distinguishable morphological and physiological evolutionary phases, which are identified by the comparative place of the kinetoplast and the scourge sing to the cell nucleus ( De Souza, 2002 – autre? ) : The trypomastigote is the extracellular extended signifier found in the craniate host, classically known as morbific signifier, which disseminate throughout the host organic structure. Its kinetoplast is situated posteriorly in relation to the karyon located in the center of the parasite and presents a big free scourge arising near the kinetoplast. The amastigote is the intracellular spherical phase in craniate cells, which multiplies by longitudinal binary fission. It displays a short discreet scourge and the kinetoplast is near the karyon. The spheromastigote is the spherical signifier found in the midgut of the bug, rather similar to amastigote but with a bigger scourge, which is the passage between the blood and vector elongated signifiers. Finally, the epimastigote is the extracellular extended signifier nowadays in the enteric piece of land and piss of the insect vector, where it besides multiplies by longitudinal binary fission. Its kinetoplast and the free scourge are located in the anterior place of the karyon ( Tyler et al. 2001, de Lana et Al. 2010 ) .

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!

order now

Infection of the craniate host is perfomed by metacyclic trypomastigotes, nowadays in the body waste of a bug, which enter through the insect bite lesion or mucosal tissues. The metacyclic signifier is able to occupy a broad scope of phagocytic and nonphagocytic nucleated cells. Invasion occurs by one of three distinguishable mechanisms after interaction parasite-host cell ( favored by several molecules like gp82 glycoprotein or sialic acid Alves and Mortara, 2009? ) . The best-studied of them is lysosome dependant: T. cruzi organizes the microtubule cytoskeleton of the host cell in order to direct recruit lysosomes to the point of parasite fond regard. These lysosomes so fuse with the plasma membrane, foremost organizing a junction with the parasite and so making a vacuolar compartment, called the parasitophorous vacuole, in which the come ining parasite transiently resides. Invasion may besides be facilitated by the host actin cytoskeleton: the parasitophorous vacuole is ab initio constructed from the plasma membrane of the host cell, which distorts in pseudopodes along the parasite and includes it. Finally, it has been proved that the parasite may come in a cell under force per unit area from its ain motility ( ref ) . However, this mechanism is thought to be the least of import mechanism of invasion. Once within the vacuole by any of these mechanisms, lysosomes continue to traffic to and blend with the parasitophorous vacuole, taking to its acidification. This induces the rapid distinction to an amastigote and activates a parasite derived porin, Tc-tox, that destroys the vacuole membrane, allowing the flight of the parasite into the cytol where the amastigote proliferates by binary fission. When the cell is filled with these signifiers, the amastigotes elongate, reacquiring their long scourge and differentiate into trypomastigotes. When the cell becomes filled with these former, the plasma membrane ruptures and important degenerative procedures can be observed, likely due to the intense motion of the parasites ( Alves and Mortara, 2009 ) . Trypomastigotes that are released outside the cell can occupy next cells or enter the blood and lymph circulation and disseminate. It is of import to observe that amastigotes are besides morbific and can be found in the blood. Both signifiers can be taken up in the blood repast of a bug, traveling to their midgut where they differentiate into amastigotes that extend their scourge to go spheromastigotes, which farther lengthen to go epimastigotes. These signifiers, that are besides able to retroflex, migrate to the insect rectum where they attach by their scourge and undergo metacyclogenesis to human morbific trypomastigote signifiers which, one time wholly transformed, are excreted with the body waste, finishing the life rhythm. ( Tyler et al. 2003 + 2001 a voir, de Lana et Al. 2010 )

Due to their deficiency of sexual reproduction, T. cruzi is non germinating like other eucaryotic species. Indeed, the generation by binary fission described above lead to phantom of homogenous line of descents isolated from each other. Six major line of descents or DTUs ( distinct typing units which can be defined as sets of stocks that are genetically closer to each other than to any other stock ) are identifiable by common molecular, familial, biochemical, or immunological markers ( Tibayrenc et al. 2010 ) . These major line of descents named T. cruzi I, IV, II, III, V and VI ( matching to the old I, IIb, IIc, IIa, IId and IIe severally ) are non homogeneously distributed in Latin America and have discriminatory hosts. However, we can happen all line of descents in worlds of all geographic portion. Many surveies have been done in order to cognize if some line of descents were more infective or lead to more complications than others but, for now, even if there are many cases of local associations between parasite genetic sciences and clinical result, no planetary correlativities have been clearly demonstrated. ( Tibayrenc et al. 2010, Macedo et Al. 2010 )

Clinic facets, diagnostic and intervention

Chagas disease has two consecutive stages, ague and chronic. The acute stage, in which the general mortality rate in nontreated persons ranges from 2 % to 12 % , lasts 6 to 8 hebdomad. Most of the septic patients retrieve an evident healthy position, come ining in the indeterminate chronic signifier, where no organ harm can be demonstrated by the current criterion methods of clinical diagnosing. While most patients remain in this signifier of the disease, 20 to 35 % of the septic persons will develop irreversible lesions of the independent nervous system in the bosom ( represents the first cause of cardiac lesions in immature grownups in the endemic states in Latin America ) , esophagus, colon, and peripheral nervous system after several old ages of the chronic stage ( Moncayo et al. 2010 ) . This chronic stage now constitutes the major job in endemic and nonendemic states. Indeed, at least 20 % of the 1000000s of Chagasic patients will develop chronic bosom or digestive disease. All of these people are possible senders of the parasite by agencies of blood and organ organ transplant, and those patients enduring Chagas bosom disease surely will hold terrible working restrictions, high costs refering medical attending, and decreased life anticipation ( Pinto Dias et Al. 2010 ) .

The diagnostic necessities have changed with the globalisation of the infection by T. cruzi in non-endemic states. Taking into history that the huge bulk of septic persons are at the chronic symptomless stage, their lone marker would be the presence of T. cruzi antibodies, with the possibilitythat the septic persons have no ailments or clinical abnormalcies. The intuition may therefore besides come from the epidemiological background of the patient ( past abode in endemic countries, household history or work with the parasite ) . Laboratory diagnosing includes parasitological and serological trials, depending on the suspected stage of the disease: parasitological trials during the acute stage or serological 1s during the chronic stage. The often used direct parasitological is the fresh blood vilification ( more sensitive than a dry vilification or a thick vilification ) . If no parasite is found, concentration techniques based on centrifugation as microhaematocrit or Strout technique are preferentially used but xenodiagnoses or hemoculture may besides been practiced, overall for chronic disease diagnostic. Finally, PCR is a rather new diagnostic tool but its specificity is non ever assured. Many different serological trials ( indirect haemagglutination trial, indirect immunofluorescence, ELISA aˆ¦ ) have been designed and the WHO recommends using at least two trials in analogue to see the diagnosing.

There are really two drugs on the market employed to bring around Chagas disease: Nifurtimox and Benznidazole which act by the production of free groups, superoxide anions, H peroxide and electrophilic metabolites ( Apt et al. 2000 ) . If these drugs bring concrete benefits for acute instances and immature chronic, surveies have established that the intervention is merely effectual for a minor proportion ( 20 % ) of chronic older persons ( Pinto Dias et Al. 2010, Apt et Al. 2010 ) . Other drugs are presently under surveies but the deficiency of biological markers of remedy for chronic disease ( serology remains sometimes positive boulder clay 20 old ages after effectual intervention and absence of parasite in blood does n’t intend absence of parasites in tissues ) makes tough their development. Importantly, since the people with Chagas disease have by and large low economic resources, large pharmaceutical companies are non interested to develop new drugs for this disease and the production of Nifurtimox and Benznidazole have even been stopped by their several houses, allowing unambiguously a Brazilian research lab green goods Benznidazole which to day of the month hold non the capacities to run into the planetary drug demand ( Apt et al. 2000 ) .

Congenital disease

Congenital disease is due to a maternal-fetal transmittal of T. cruzi unrecorded parasites that took topographic point in utero ( antenatal transmittal ) or at the clip of bringing ( perinatal transmittal ) that persist after birth. It therefore excludes the “ postpartum ” transmittal of parasites ( chiefly through maternal milk by breast-feeding ) and the transmittal of dead parasites or parasite Deoxyribonucleic acid. Even if inborn T. cruzi infection is an acute infection, most of instances are symptomless ( ref ) . However, non-specific clinical manifestations like febrility, low birth weight ( less than 2500 g ) , prematureness, hepato-splenomegaly, pneumonitis and, more seldom, icterus can happen ( ref ) .

The transmittal rate, defined as the ratio between the figure of inborn instances and the figure of septic female parents, is described to be between 1 % and 12 % , depending of the geographic parts and the diagnostic trial used ( Carlier and Torrico, 2003 ) . In contrast to other inborn transmittal like toxoplasmosis or CMV, transmittal of T. cruzi can happen in both ague and chronic stages of maternal infection and therefore be repeated at each gestation ( Carlier and Torrico, 2003 ) during all of the fertile period of a adult female ‘s life ( Carlier and Torrico, 2003 ) . This affair of fact induces that, even if other transmittal ways are eradicated, transgenerational transmittal of parasites can prevail during several other decennaries in endemic every bit good as in nonendemic countries. This high spots that inborn infection with T. cruzi as an of import public wellness job that can easy widen in infinite ( through migrations ) and clip ( Carlier and Torrico, 2003 ) .

The inborn transmittal is described to be largely transplacental, infecting trophoblastic beds or other placental tissues like fringy zone, mesenchymal tissues and eventually making foetal vass embedded in such tissue. Surveies have besides pointed the possibility of an infection through parasites released into amnionic fluid polluting foetuss by unwritten or pneumonic paths but antimicrobic peptides usually contained in amnionic fluid ( Akinbi et al. , 2004 ) do this untypical. ( Carlier et al. 2010 )

The chief factors that license happening and development of a inborn infection are the parasite itself, the female parent and the foetal capacity to react to parasite invasion. Up to day of the month, there is no relationship between T. cruzi line of descents ( A§2.7.2 ) and inborn infection in worlds ( Virreira et al. 2006 ) . Besides, since 53 % of pregnant adult females exposing high parasitaemia transmitted the parasite for merely 1-12 % of inveterate septic adult females in which blood parasites are barely noticeable ( ref? 22.2.1 to see – inquire YC ) and the rate of hemoculture positive is double higher in inveterate septic female parents conveying parasites than in untransmitting 1s ( Hermann et al. 2004 ) , parasitaemia in pregnant adult females seems to be an of import factor lending to inborn transmittal of T. cruzi ( Carlier et al. 2010 ) . Quite related to this, it has been proved that a tinier IFN-i?§ production by T cells of the female parent correlative with a higher hazard of parasite transmittal to their foetus, surely due to a higher parasitaemia ( Hermann et al. 2004 ) . In general, a good immune response from the female parent against the parasite ( A§ 2.8 ) license a lessening in the hazard of transmittal. Other maternal factors such as immature age and/or primiparity, and/or malnutrition and poorness besides favor the inborn transmittal of T. cruzi ( ref ) . Finally, the foetus itself can lend to halt the inborn infection. Indeed, it has been shown that clean newborns born to infected female parents produce inflammatory cytokines at a higher rate than infected 1s ( Vekemans et al. 2000 ) and it is thought that parasite, opsonized by transferred maternal antibodies, can be eliminated by their activated monocytes ( A§ 2.8.3 ) ( Carlier et al. 2010 ) .

Since a kid born with inborn Chagas disease, whatever the neonatal morbidity, is at hazard to develop into chronic determinate disease in ageing and the intervention of really immature babies with Benznidazole and Nifurtimox is really effectual ( 90 – 100 % of remedy, Apt et Al. 2010, Carlier et Torrico 2003 ) , it is of the highest importance to observe the infection. In order to execute this, a systematic showing of the female parents has to be effected serologically and, if this trial is positive, research of unrecorded trypomastigotes at birth and of specific-antibodies after 8 months of age have to be performed.

de Lana et Al. 2010 – Biology of Trypanosoma cruzi and Biological Diversity. American Trypanosomiasis Chagas Disease. Department of the interior: 10.1016/B978-0-12-384876-5.00014-9

Pinto Dias et Al. 2010 – Social and Medical Aspects: Morbidity and Mortality in General Population. DOI: 10.1016/B978-0-12-384876-5.00003-4

Moncayo et Al. 2010 – Current Tendencies and Future Prospects for Control of Chagas Disease. Department of the interior: 10.1016/B978-0-12-384876-5.00004-6

Tibayrenc et Al. 2010 – Reticulate Evolution in Trypanosoma cruzi: Medical and Epidemiologic Implications. Department of the interior: 10.1016/B978-0-12-384876-5.00019-8

Macedo et Al. 2010 – Deductions of Trypanosoma cruzi Intraspecific Diversity in the Pathogenesis of Chagas Disease. Department of the interior: 10.1016/B978-0-12-384876-5.00020-4

Apt 2000 – Treatment of Chagas Disease. Department of the interior: 10.1016/B978-0-12-384876-5.00030-7

Carlier et Al. 2010 – Maternal-Fetal Transmission of Trypanosoma cruzi DOI: 10.1016/B978-0-12-384876-5.00022-8

Ops 2006 – Estimacion cuantitativa de la enfermedad de Chagas en La americas.

Akinbi et Al. 2004 – Host defence proteins in vernix caseosa and amnionic fluid

Hermann et Al. 2004 – Congenital transmittal of Trypanosoma cruzi is associated with maternal enhanced parasitaemia and reduced production of interferon-gamma in response to parasite antigens

Carlier et Torrico 2003 – Congenital infection with Trypanosoma cruzi: from mechanisms of transmittal to schemes for diagnosing and control.

Virreira et Al. 2006 – Congenital Chagas disease in Bolivia is non associated with DNA polymorphism

of Trypanosoma cruzi

Tyler et Al. 2003 – The Life Cycle Of Trypanosoma Cruzi DOI: 10.1007/978-1-4419-9206-2_1

Alves and Mortara 2009 – A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?


I'm Niki!

Would you like to get a custom essay? How about receiving a customized one?

Check it out