Immunological response to re-infections with clones of the Colombian strain of Trypanosoma cruzi with different degrees of virulence: influence on pathological features during chronic infection in mice

Re-infections with Trypanosoma cruzi are an aggravating factor for Chagas disease morbidity. The Colombian strain of T. cruzi represents multiclonal populations formed by clonally propagating organisms with different tropisms and degrees of virulence. In the present study, the influence of successive inoculations with clones of the Colombian strain, exhibiting different degrees of virulence, on chronic myocarditis and the humoral and cellular immune responses (Col-C1 high virulence, Col-C8 medium virulence and Col-C5 low virulence) were demonstrated. Mice from three groups with a single infection were evaluated during the acute (14th-30th day) and chronic phases for 175 days. An immunofluorescence assay, ELISA and delayed type hypersensitivity (DTH) cutaneous test were also performed. Mice with a triple infection were studied on the 115th-175th days following first inoculation. The levels of IgM and IgG2a were higher in the animals with a triple infection. DTH showed a higher intensity in the inflammatory infiltrate based on the morphometric analysis during a 48 h period of the triple infection and at 24 h with a single infection. The histopathology of the heart demonstrated significant exacerbation of cardiac inflammatory lesions confirmed by the morphometric test. The humoral responses indicate a reaction to the triple infection, even with clones of the same strain.

Myocarditis associated with Plasmodium vivax malaria: a case report

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

An unusual case of heart failure due to Plasmodium vivax infection with a favorable outcome

Although malaria is one of the oldest types of parasitic infection, we have recently witnessed substantial changes in the outcome of malarial infections. Severe Plasmodium vivax infections have recently become more frequent, and are occasionally associated with fatal outcomes. Cardiac arrhythmia and myocardial failure have also been reported, typically in association with Plasmodium falciparum infections. We report a case of myocarditis and heart failure, due to Plasmodium vivax infection, along with the favorable outcome.

Manifestaciones cardiovasculares de la toxocariasis humana / Cardiovascular manifestations of human toxocariasis

La toxocariasis es una infección parasitaria producida por un helminto que en el ser humano no alcanza su estadio adulto. El hombre es para sus especies, Toxocara canis y Toxocara cati, un hospedador paraténico. Dicha infección puede producir el síndrome de larva migrans visceral, el síndrome de larva migrans ocular y la toxocariasis inaparente. En el síndrome de larva migrans visceral el compromiso de órganos puede incluir hígado, pulmón, piel, sistema nervioso, musculoesquelético, riñón y corazón. Sobre este último, cada vez se reconoce más la importancia que pueden tener las manifestaciones cardiovasculares de la toxocariasis y la relevancia clínica de considerarlas. En el presente artículo, haciendo una búsqueda sistemática de información, se revisan los principales aspectos clinicopatológicos de las manifestaciones cardiovasculares de la toxocariasis incluyendo su fisiopatología, hallazgos de laboratorio, diagnóstico y opciones terapéuticas, con el objeto de llamar la atención acerca de la importancia de esta zoonosis y su relevancia para la medicina cardiovascular en adultos y en niños.

Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxoca-riasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors: how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Papel do óxido nítrico no desenvolvimento de lesões cardíacas na fase aguda da infecção experimental pelo Trypanosoma cruzi / Role of nitric oxide in the development of cardiac lesions during the acute phase of experimental infection by Trypanosoma cruzi

A doença de Chagas é causada pelo Trypanosoma cruzi e o coração é o órgão mais acometido. O óxido nítrico apresenta importante ação anti-Trypanosoma, porém, com pouca evidência de seu papel no mecanismo de lesão tecidual. O objetivo deste estudo foi analisar a contribuição do óxido nítrico no desenvolvimento da inflamação e da fibrose cardíaca na fase aguda da infecção experimental por cepas Y e Colombiana do Trypanosoma cruzi. A inflamação foi significativamente maior nos animais infectados pela cepa Colombiana, comparada com os infectados com a cepa Y, tanto nos animais C57BL/6 (3,98x1,87 por cento; p=0,004) quanto nos animais C57BL/6 deficientes na sintase do óxido nítrico induzível (3,99x2,4 por cento; p=0,013). O parasitismo cardíaco dos animais C57BL/6 deficientes na sintase do óxido nítrico induzível infectados pela cepa Colombiana foi significativamente maior que o destes mesmos animais infectados com a cepa Y (2,78x0,17 ninhos/mm²; p=0,004) assim como, os animais C57BL/6 infectados com a cepa Colombiana (2,78x1,33 ninhos/mm²; p=0,006) ou cepa Y (2,78x0,53 ninhos/mm²; p=0,005). Os dados reforçam o papel do óxido nítrico no controle do parasitismo e sugerem seu papel na proteção tecidual, controlando a inflamação e potencialmente diminuindo lesões cardíacas durante a fase aguda na doença de Chagas experimental.

Chagas disease is caused by Trypanosoma cruzi and the heart is the organ most affected. Nitric oxide has notable anti-Trypanosoma action, but with little evidence regarding its role in the mechanism for tissue injury. The objective of this study was to analyze the contribution of nitric oxide towards the development of inflammation and cardiac fibrosis during the acute phase of experimental infection by Y and Colombian strains of Trypanosoma cruzi. The inflammation was significantly more intense in animals infected with the Colombian strain, compared with those infected with the Y strain, both in C57BL/6 animals (3.98 vs 1.87 percent; p = 0.004) and in C57BL/6 animals deficient in inducible nitric oxide synthase (3.99 vs 2.4 percent; p = 0.013). The cardiac parasite load in inducible nitric oxide synthase-deficient C57BL/6 animals infected with the Colombian strain was significantly greater than in those infected with the Y strain (2.78 vs. 0.17 nests/mm²; p = 0.004), and also significantly greater than in the C57BL/6 infected with both the Colombian strain (2.78 vs 1.33 nests/mm²; p = 0.006) and Y strains (2.78 vs 0.53 nests/mm²; p = 0.005). The data confirm that nitric oxide has a role in parasite load control and suggest that it has a role in tissue protection, through controlling inflammation and potentially reducing cardiac lesions during the acute phase of Chagas disease.

Reinfections with strains of Trypanosoma cruzi, of different biodemes as a factor of aggravation of myocarditis and myositis in mice

Reinfeccões pelo Trypanosoma cruzi em pacientes de áreas endêmicas têm sido mencionadas como fator agravante das manifestacões cardíacas na doenca de Chagas. No presente estudo, a influência da tríplice infeccão com cepas de diferentes biodemas, sobre as lesões do miocárdio e de músculo esquelético foi investigada experimentalmente. Cinqüenta e oito camundongos cronicamente infectados com a cepa Colombiana do Trypanosoma cruzi (Biodema Tipo III) foram sucessivamente reinoculadas como a seguir: 1º grupo - reinfectados com a cepa 21 SF (Tipo II) seguido pela cepa Y (Tipo I); 2º grupo - reinfeccão com a cepa Y seguida pela cepa 21SF. A análise isoenzimática dos parasitas das hemoculturas obtidas dos animais com tríplice infeccão, revelou os padrões dos diferentes zimodemas no mesmo animal. Cada cepa do Trypanosoma cruzi foi re-isolada após quatro passagens em camundongos no 7º, no 14º, ou no 30º dia após a inoculacão com o sangue de camundongos com tríplice infeccão. Resultados da histopatologia demonstraram uma significante exacerbacão das lesões inflamatórias de miocárdio e músculo esquelético, confirmadas pela avaliacão morfométrica. Não foi detectada acentuacão do parasitismo. A possibilidade de aumento da resposta celular nos animais com tríplice infeccão é sugerida.

CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

The comprehension of the pathogenesis of Trypanosoma cruzi-elicited myocarditis is crucial to delineate new therapeutic strategies aiming to ameliorate the inflammation that leads to heart dysfunction, without hampering parasite control. The augmented expression of CCL5/RANTES and CCL3/MIP-1alpha, and their receptor CCR5, in the heart of T. cruzi-infected mice suggests a role for CC-chemokines and their receptors in the pathogenesis of T. cruzi-elicited myocarditis. Herein, we discuss our recent results using a CC-chemokine receptor inhibitor (Met-RANTES), showing the participation of CC-chemokines in T. cruzi infection and unraveling CC-chemokine receptors as an attractive therapeutic target for further evaluation in Chagas disease.

Detection of myocarditis in chagasic patients by 99mTc-mononuclear leukocytes (preliminary results)

Successive periods of reactivation of Trypanosoma cruzi in the myocardium may contribute to chronic, progressive myocardial damage and fibrosis, indicating that viable parasites are still present in the host, although the infection may remain quiescent or inapparent. Identifying the presence of active infection as well as the intensity of the inflammatory process can lead to the administration of more effective chemotherapeutic agents to exterminate the parasite. We investigated the use of Tc-99m-mononuclear leukocytes as a complementary tool for the diagnosis of active chagasic myocarditis. Using the stannous chloride labeling method, previously reported by us, 22 patients underwent Tc-99m-leukocyte scintigraphy. Planar images were obtained after 30 minutes, 3 and 24 hours of endovenous administration of approximately 444MBq (12 mCi) of the labeled cells. There was abnormal cardiac uptake in 3 of the 22 patients. These findings suggest the presence of markedly Chagas' disease activity with important clinical implications.

Occurrence of myocarditis in rodents infected with Schistosoma mansoni.

Myocarditis is a complication of Schistosoma mansoni infection, although the literature does not provide much information regarding the frequency of myocarditis. In order to analyze the relationship between myocarditis and S. mansoni infection, different laboratory animals were infected with different dose of cercariae. At different weeks of post infection the hearts of infected animals were collected and processed for histopathological examination. Myocarditis was characterized by interstitial inflammatory cell infiltration with or without granuloma. ddY and ICR infected mice showed eosinophilic egg-granuloma in the heart where as neither eosinophil nor egg-granuloma were observed in the heart of infected gerbils. Higher number of eosinophils and greater size of the granuloma were found in the ddY mice than ICR mice. The number of eosinophils was significantly higher in severe myocarditis. Incidence of myocarditis was higher in ddY mice (69% with 100) than ICR mice (35%) and gerbils (23%). The results indicate that ddY mice were more susceptible to S. mansoni infection in the development of myocarditis and myocardial severity was associated with greater eosinophil infiltration. These findings suggest that eosinophils might be involved in the development of myocarditis, although the involvement of immunological reaction can not be ruled out.

Pathogenesis of chagasic myocarditis: an experimental study

Com a finalidade de estudar a patogenia da miocardite chagasica , foram inoculados camundongos brancos com a cepa Y do Trypanosoma cruzi. Os animais, após o controle da parasitemia, foram sacrificados: a)para a fase aguda (primeiros 30 dias), cinco animais diariamente; b)sub-aguda (do trigesimo dia e nonagesimo dia), cinco animais semanalmente e c)crônica, os sobreviventes com 365 dias após inoculacao. A parasitemia surgiu no sexto dia e aumentou progressivamente até atingir o seu nível máximo na terceira ou quarta semana, decrescendo a seguir ate o trigésimo dia, desaparecendo do sangue circulante após o octogesimo sétimo dia. O parasitismo acompanhou a parasitemia, porém sem relaçäo quantitativa...

Cardiac plexus of dogs experimentally infected with Trypanosoma cruzi: inflammatory lesions and quantitative studies

Qualitative and quantitative aspects of the superficial and profound cardiac plexus of dogs experimentally infected with Be-62 and Be-78 strains of Trypanosoma cruzi were studied. Animals were autopsied in the acute phase ofinfection. The inflammatory process, lesions and number of parasites were more intense and frequent in animals infected with the Be-78 strain than in those infected with Be-62. espite this, no statistically significant differences could be found between the number of neuron bodies in the ganglia of infected and control dogs.

Correlação clinicopatológica de 50 casos de síndrome de imunodeficiência adquirida: estudo retrospectivo / Clinicopathologic Correlation in 50 Cases of Acquired Immunodeficiency Syndrome. Retrospective Study

PURPOSE--To analyze myocardial abnormalities in patients of acquired immunodeficiency syndrome with clinical and pathological correlation. METHODS--We selected 50 cases, retrospectively, age ranged from 3 months to 40 years, all of them had myocardial changes and the data of clinical records fulfilled our protocol. Cases of others cardiac diseases were not included. RESULTS--The pathological findings were: myocarditis in 33 (11 had severe myocarditis) and degenerative hystological lesions in 17. The etiologic agents detected were: Toxoplasma in 11, Cryptococcus in 7 and Cytomegalovirus in 3. In 12 cases we could not find any agent. In 15 cases occurred others lesions: endocarditis, pericarditis and sarcoma of Kaposi. It was noted tachycardia in 15 cases, decrease of heart sounds in 12, arterial hypotension in seven, systolic murmur in 8, galop rhythm in 7, pericardial friction rub in 3, arrhythmia in 2. Four patients had congestive heart failure. The EKG showed sinus tachycardia in 18, ST and T changes in 10, low voltage in 5, ST segment elevation in 5 and extrasystoles in 3 cases. The echocardiogram findings were: pericardial effusion in 9 cases and 9 had ventricular dysfunction. CONCLUSION--The cardiac lesions were very important even in patients without clinical signals. We need others prospective studies with viral identification trying to detect specific lesions of HIV

Objetivo - Analisar as alterações miocárdicas na síndrome da imunodeficiência adquirida e correlacionar os achados clínicopatológicos. Métodos - Foram selecionados, retrospectivamente, 50 pacientes entre 4 meses e 40 anos de idade, que apresentavam lesões miocárdicas à histologia e cujos prontuários continham os dados do protocolo. Foram in cluídos aqueles com lesões cardíacas de outra etiologia. Resultados - Os achados anatomopatológicos foram miocardite em 33 (66%) casos, sendo grave em 11 e lesões degenerativas em 17. Os agentes etiológicos foram Toxoplasma em 11, Criptococcus em 7, Citomegalovírus em 3 e inespecífica em 12. Em 15 casos havia também outras lesões como endocardite, pericardite e sarcoma de Kaposi. Quanto aos achados clínicos observamos taquicardia em 15 casos, hipofonese de bulhas em 12, hipotensão arterial em 7, sopro sistólico em 8, ritmo de galope em 7, atrito pericárdico em 3 e arritmia cardíaca em 2. Quatro pacientes tiveram sinais de insuficiência cardíaca congestiva. O ECG mostrou taquicardia sinusal em 18, distúrbio de repolarização em 10, baixa voltagem em 5, supradesnivelamento de ST em 5 e extra-sistolia em 3. Ao ecocardiograma 9 apresentaram derrame pericárdico e 9 diminuição de contratilidade ou da função ventricular. Conclusão - As lesões cardíacas foram expressivas mesmo em pacientes sem sinais clínicos para tal. São necessários mais estudos com métodos de identificação viral para tentar detectar as lesões miocárdicas pelo HIV.

Miocardite por toxoplasma gondii em homem com síndrome de imunodeficiência adquirida / Myocarditis due to toxoplasma gondii in a man with acquired immunodeficiency syndrome

Homem de 26 anos, portador de síndrome de imunodeficiência adquirida, com quadro neurológico focal, desenvolveu sinais clínicos de falência do miocárdio e ecocardiograma com sinais de disfunçäo ventricular, evoluindo para morte súbida. O exame anátomo-patológico do coraçäo demostrou alteraçöes degenerativas de fibras musculares, infiltrados focais linfohistiocitários e presença de T. gondii

Estudo parasitológico e anátomo-patológico da fase aguda da doença de Chagas em cäes inoculados com duas diferentes cepas do Trypanosoma cruzi / A parasitological and pathological study of the acute phase of Chagas' disease in dogs inoculated with 2 different strains of Trypanosoma cruzi

Cäes jovens foram infectados com as cepas Y e CL do T. cruzi usando-se como inóculos 10**7 formas sangüíneas inoculadas por via intraperitoneal e 2x10**3 tripomastigotas metacíclios obtidos do inseto vetor e inoculados por via conjuntival. As cepas Y e CL induziram nos cäes curvas de parasitemia totalmente distintas, confirmando dados parasitológicos obtidos em camundongos e coelhos. Com a cepa CL a parasitemia, com ambos os inóculos, foi gradualmente ascencional ao passo que com Y a parasitemia foi extremamente baixa, irregular e, com freqüência, subpatente. Com ambas as cepas o parasitismo e as lesöes predominaram no miocárdio. Entretanto, com a cepa Y a miocardite foi sempre intensa desde as fases mais precoces da infecçäo, ao passo que com a cepa CL o processo inflamatório tornou-se acentuado somente a partir do 20§ dia. Freqüentemente a intensidade da miocardite observada em alguns animais näo guardava relaçäo com a parasitemia; em alguns cäes com parasitemia subpatente, nos quais a infecçäo só foi diagnosticada pelo xenodiagnóstico, a intensidade da miocardite foi comparável àquela observada nos animais com parasitemia patente. Idêntica correlaçäo também näo foi assinalada em relaçäo ao parasitismo tissular. Esses achados sugerem a participaçäo de mecanismo imunológicos na gênese das lesöes, ainda na fase aguda da infecçäo