Archive for the ‘Chagas Disease In Children’ Category

Pathology Chagas Disease

INTRODUCTION:

Chagas disease (also known as American trypanosomiasis) is produced by the hemoflagellate protozoan Trypanosoma cruzi. Chagas disease is transmitted via the bite of the reduviid bug, also known as the triatomine insect or “kissing bug”. In Latin America, recent estimates indicate an infection prevalence of 13 million and an annual incidence of 200,000 cases in 15 countries. Formerly considered a rural disease, Chagas disease is now ubiquitous because of changes in the social patterns in most countries, mainly a result of rural-urban migration . Chagas disease also occurs in nonendemic areas where it may be acquired by blood transfusion, congenital transmission and organ transplantation .

The major morbidity associated with this disease is threefold: cardiac disease, megaesophagus, and megacolon. Cardiac involvement is characterized by myocarditis and ultimately a dilated cardiomyopathy that becomes evident years after infection. The infection can cause greater morbidity in individuals co-infected with HIV.

The pathology and pathogenesis of Chagas disease will be reviewed here. Cardiac and gastrointestinal manifestations and the epidemiology and control of the infection are discussed separately. (See “Clinical manifestations and diagnosis of Chagas heart disease” and “Treatment and prognosis of Chagas heart disease” and “Evaluation and management of gastrointestinal Chagas disease” and “Epidemiology and control of Chagas disease”.

Symptoms and Pathology of Chagas’ disease:

Metacyclic epimastigotes of T. cruzi, secreted by the triatomine bug while taking a blood meal, are rubbed into the wound by the victim. Trypanosomes are taken up by macrophages and multiply intracellularly as amastigotes in the cytoplasm of the host cells. When these cells are loaded with amastigotes the latter transform to trypamastogotes and the host cells bursts open, releasing the trypamostigotes into the circulating blood, causing high parasiteamia and fever. These are the symptoms of the early stage of Chagas’ disease. When antibodies against the trypomastigotes develop parasiteamia goes down and the trypomastigotes almost completely disappear from the blood to such a level that they cannot be detected other than by xenodiagnosis or by such sophisticated techniques as PCR (polymerase chain reaction).

The Human Immune Response System:

The human immune response system recognizes pathogensT cells and antigens and acts to remove, immobilize, or neutralize them. The immune system is antigen-specific (responding to specific molecules on a pathogen) and has memory (its defense to a pathogen is encoded for future activation). The immune system relies on several components to fight an infecting pathogen. T cells are lymphocytes that circulate between the blood, lymph, and lymphoid organs to trigger a systemic immune response with antigen-receptors on the T cell membrane. B cells are lymphocytes that activate the primary immune response when antigens bind to their receptors, causing the B cells to proliferate. Daughter cells of B cells later differentiate into antibody-releasing plasma cells. B cells also comprise the immune system’s memory (see diagram).
Antibodies, also called immunoglobulins, are divided into five classes by structure and function, enabling them to recognize a wide spectrum of antigens. Antibody functions include complement fixation that can lead to antigen-cell lysis (rupture) and can cause inflammation. Antibodies also generate a neutralization response where viruses and bacteria are destroyed by phagocytes. Agglutination, or clumping together, of foreign cells are caused by B cells’ promotion of complex cross-linking of antibodies binding to antigens. These agglutinated cells are phagocytized. B cells are cloned in massive quantities for a single specific antigen.

ABSTRACT

Trypanosoma cruzi acute infections often go unperceived, but one third of chronically infected individuals die of Chagas disease, showing diverse manifestations affecting the heart, intestines, and nervous systems. A common denominator of pathology in Chagas disease is the minimal rejection unit, whereby parasite-free target host cells are destroyed by immune system mononuclear effectors cells infiltrates. Another key feature stemming from T. cruzi infection is the integration of kDNA minicircles into the vertebrate host genome; horizontal transfer of the parasite DNA can undergo vertical transmission to the progeny of mammals and birds. kDNA integration-induced mutations can enter multiple loci in diverse chromosomes, generating new genes, pseudo genes and knock-outs, and resulting in genomic shuffling and remodeling over time. As a result of the juxtaposition of kDNA insertions with host open reading frames, novel chimeric products may be generated. Germ line transmission of kDNA-mutations determined the appearance of lesions in birds that are indistinguishable from those seen in Chagas disease patients. The production of tissue lesions showing typical minimal rejection units in birds’ refractory to T. cruzi infection is consistent with the hypothesis that autoimmunity, likely triggered by integration-induced phenotypic alterations, plays a major role in the pathogenesis of Chagas disease.