American Trypanosomiasis (Chagas Disease)

2- American trypanosomiasis (Chagas’ disease)  Causative agent: Trypanosoma cruzi Geographic distribution/epidemiology  The agents of disease are distributed from southern regions of the USA, via Mexico and Central America to South America until Argentina and Northern Chile  About 50 million people are infected  New infections become reduced due to large bug-control programs in rural regions Biology, morphology Trypomastigote (Trypanosoma cruzi) The trypomastigoteis found in the bloodstream of infected vertebrates It often has a characteristic ‘C’ shape in Giemsa stains of bloodsmears The large kinetoplast is found at the posterior end of the cell Life cycle  Humans and a broad spectrum of animals belonging to a sylvatic cycle such as rodents, monkeys, cats, dogs, opossum, armadillo, etc. are infected during blood sucking of reduviid bugs belonging to the genera Rhodnius, Triatoma, Dipetalogaster Vectors: Reduviid bugs (Rhodnius, Triatoma, Dipetalogaster) = Kissing bugs or con-nose bugs Resorvire hoss: opossum, armadillo, cats, dogs, rodents  In contrast to African trypanosomes, the transmission of stages of T. cruzi does not occur via injection of saliva of the tsetse flies but occurs when parasites, which are included in droplets of bug feces, are rubbed into the wounds at biting sites of the bugs Then occur in the blood of human’s metacyclic trypomastigote stages, which appear C- or S-like shaped and reach a length of 15–20 μm  Metacyclic trypomastigote enter in human macrophages, muscle (heart) and nerve cells, where they are situated directly inside the cytoplasm. Penetrated trypomastigotes are transformed into amastigotes (short mastigotes), which start binary fissions and finally become again trypomastigotes. Such infected host cells were called pseudocysts, which finally become disrupted, thus setting these trypomastigotes free, which again enter neighbouring cells (in the heart) and are also destroyed This constant destruction leads finally (mostly after years) to the death of humans.  This mostly intracellular parasitism leads to the fact that immune reactions are low and thus infections with T. cruzi remain often undetected for years  Bugs engorge (swallow) such trypomastigotes during their blood meal, these stages become attached at their intestinal wall, develop into epimastigotes and introduce repeated binary fissions In the terminal region of the intestine of the bugs again, stage transformation occurs and finally infectious metacyclic trypomastigotes occur, which then are transmitted to humans or to other vertebrate hosts within a droplet of the bug’s feces  These infectious stages inside the hind gut of the vector bug are described as metacyclic stages Symptoms of the disease (Chagas’ disease, American trypanosomiasis):  This disease is divided into an acute and a chronic phase Acute phase:  After introduction of the trypomastigotes (e.g. by skin scratching at the biting site of the bugs) into the body of a human or animal host, the parasitic stages become reproduced by repeated binary fissions in close nearness of the biting site. This increasing amount of parasites leads to a strong inflammation reaction, which is called chagoma and is often found close to the eyes Typical symptoms are reddening and swelling of the cheek, the eyelids and conjunctiva (Romana sign) Also the preauricular lymph nodes may increase  After a 1–3 weeks long incubation period, the haematogenous distribution of the trypomastigotes is initiated.  This phase is characterized by fever, lymph node swellings, hepatosplenomegalia and oedemas in the face and along the leg  Especially in children myocarditis and meningoencephalitis may occur in an early phase of the disease and may lead to a quick death  In general most symptoms are reduced or even absent in the following months/years, although blood stages can still be diagnosed in Giemsastained blood smears  Chronic phase:  In the chronic phase of the Chagas’ disease, which may run symptomless for many years (also called intermediate phase), parasitic stages appear rather seldom in the peripheral blood, since they reproduce themselves intracellularly inside host cells until lesions inside organs become obvious  Various types of host cells are damaged in addition to nerves leading to severe disturbances of the electrocardiogram Cardiomyopathy often occurs, which is found mainly in the right ventricle. Acute and chronic inflammations in combination with fibrinozation often introduce cardiomegaly and neurisms inside the heart tip  The congestive cardiomyopathy leads finally within a few months to death Lesions of the nerve system introduce arrhythmic transmissions of stimuli, which also can initiate sudden complete heart dysfunction. The destruction of nerve cells by parasites destroys nerve cells of many organs such as oesophagus, colon, kidneys, spleen, etc. and introduces formation of megaoesophagus, megacolon, etc. leading to dysphagia and obstipation. Such persons may die due to pneumonia and/or ileus obstipation. Diagnosis: 1) Definitive diagnosis of T. cruzi infection must be based on demonstration of the parasites  In young children they may be detected in the blood with ease, particularly at the height of the acute stage In older children and adults, the parasites are frequently very difficult to find. They may be demonstrated by special concentration techniques, by culture, or by the method of xenodiagnosis, which is the feeding of laboratory-reared reduviid bugs on a patient suspected of having Chagas’ disease and, after a time, examining the bugs for T. cruzi • Xenodiagnosis helps in about 50% of human infections Biopsy of enlarged lymph nodes may reveal parasites in the amastigote stage 2) Serological investigations Different types of serologic tests (e.g. IFT, ELISA, KBR, IHA, direct agglutination) show IgG antibodies in about 95% of infected persons in the chronic phase of the infection, while during the acute phase, IgM antibodies were seen The Machado-Guerreiro test is a complement fixation test using T. cruzi antigen (in chronic phase) 3) PCR: PCR gives excellent results also during the chronic phase of the disease, but is, however, not available everywhere Pathway of infection: Infected bugs discharge during or after a blood sucking at human skin a droplet of feces containing infectious stages, which are rubbed into the biting site during scratching Prophylaxis: Bug control in houses with the help of insecticides Therapy: Very difficult; Nifurtimox (Lampit) (drug of choice) during the chronical phase: 8–10 mg/kg bodyweight is recommended for adults (in three divided doses) for 90 days; children should get higher doses (15–20 mg) for 90 days divided into four daily portions Treatment should be done in the hospital Benznidazole (Radanil or Rochagan) is effective when given 5–7 mg/kg bodyweight in two divided portions for 60 days, while children should get daily 10 mg in the same way Trypanosoma rangeli Trypomastigote stages are transmitted by the vector by its saliva while biting (salivary infection) to human hosts (kissing bugs of the genus Rhodnius: R. prolixus) Human cases of an apparently asymptomatic trypanosomal infection have been reported from Brazil, Venezuela, Colombia, Panama, El Salvador, Costa Rica, Honduras, and Guatemala  The organism has been known as Trypanosoma ariari and T. guatemalensis but seems to be correctly named T. rangeli In Panama, T. rangeli is found six times more frequently than T. cruzi, in a population in which the average combined infection rate is 3.4% Trypanosoma rangeli They are about 30 μm in length (T. cruzi stages measure only 20 μm), with a nucleus anterior to the middle of the body and a tiny kinetoplast (T. cruzi kinetoplast is large) They multiplicate in the blood fluid (not inside cells) by repeated longitudinal division T. cruzi T. rangeli An intracellular amastigote state of T. rangeli has been described from the tissues of experimentally infected suckling mice. Natural infections have been found in dogs, and T. rangeli will multiply in a number of laboratory, domestic, and wild animals, apparently none of which develop disease The diagnosis of T. rangeli infection is made by the identification of trypanosomes in stained blood films. In contrast to the other American trypanosome, T. cruzi, in which the kinetoplast is quite large, that of T. rangeli is small and inconspicuous T. rangeli infections are most common in persons less than 16 years old, being encountered in some 75% of that age group It is transmitted directly by the bite of the reduviid bug Rhodnius prolixus and a few related species No evidence of pathogenicity has been noted in any of the natural infections or in human volunteers The parasites may be isolated from the bloodstream for some months after infection Xenodiagnosis is highly recommended because there are only few parasites present in the blood