Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in the intragastric experimental infection

Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes of acute infection were observed in areas devoid of domiciled insect vectors. Considering that the distribution of T. cruzi biodemes differs in sylvatic and domestic cycles, results of studies on biodemes can be of interest regarding oral transmission. The infectivity of T. cruzi strains of different biodemes was tested in mice subjected to infection by the digestive route (gavage). Swiss mice were infected either with the Peruvian strain (Biodeme Type I, Z2b) or the Colombian strain (Biodeme Type III, Z1, or T. cruzi I); for control, intraperitoneal inoculation was performed in a group of mice. The Colombian strain revealed a similar high infectivity and pathogenicity when either route of infection was used. However, the Peruvian strain showed contrasting levels of infectivity and pathogenicity, being high by intraperitoneal inoculation and low when the gastric route was used. The higher infectivity of the Colombian strain (Biodeme Type III) by gastric inoculation is in keeping with its role in the epidemic episodes of acute Chagas disease registered in the literature, since strains belonging to Biodeme III are most often found in sylvatic hosts.

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

In order to evaluate the potential allergenicity of Blomia tropicalis (Bt) antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT) as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.

Leishmanicidal activity of Echinaster (Othilia) echinophorus crude extract

In this study, a methanolic extract from Echinaster (Othilia) echinophorus was evaluated for activity against Leishmania amazonensis. The extract showed activity against the promastigote and amastigote forms with IC50 values of 62.9 and 37.5 μg.mL-1 respectively. This extract showed a moderate toxicity on macrophages from BALB/c mice. A dose of 100 mg/kg/day was effective when administered during 15 days by intraperitoneal route to BALB/c mice infected experimentally.

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.

Efecto de la temperatura de la piel en la leishmaniasis cutanea experimental

The literature on the thermosensitive properties of strains or species of Leishmania and of other miercorganisms is revised. Cutaneous or mucocutaneous strains that infect animais in the coldest areas of the skin or mucosa in general can not grow in tissue culture at 37°C or higher temperatures and their respiratory metabolism decreases at these temperatures. These facts suggest a thermosensitive event in some important metabolism phase of the organisme. The strains or species that are able to produce visceral leishmaniasis were probably originated from cutaneous strains after genetioally determined physiological adaptation, to warmer temperatures. These strains can not only visceralize in animais and man but will also grow in tissue culture at 36-37°C and the respiratory metabolism will be higher at such temperatures. There are reasons to believe that intermediate strains, i. e., with properties of both groupsí do exist. A thermosensitive physiological event is a more general phenomenon and examples of it can also be found in the fields of virology, bacteriology and mycology. It has practical applications since some of the diseases produced by these agents can be cured by treatments with heat or artificial fever. Experiments along these line were performed on hamsters with a Costa Rican strain of L. braziliensis as an experimental model. Even after intraperitoneal inoculation lesions appear in the nose, ears, paws and tail with a subcutaneous temperature bellow 33°C at 22-24°C. Healing of the lesión is accomplished by increasing room temperature. A good lesión is produced in the rump of the animal if the area is depilated (comercial cream depilatory) previously and the naked skin cooled artificially. Elevated temperature, or the growing back of the hair will tend to diminish or cure the lesion.

Infecção experimental do camundongo albino pelo Schistosoma mansoni. I - Estudo comparativo da eficácia de diferentes vias de infecção

O presente trabalho tem por objetivo o estudo da eficácia comparativa de diferentes vias de infecção na equistossomose experimental do camundongo albino. Foram utilizados trinta camundongos albinos de ambos os sexos, com idade de dois meses, infectados com cerca de cem cercárias cada um e sacrificados três meses após a infecção. As vias de penetração empregadas foram: oral, transcutânea (por submersão parcial, imersão apenas da cauda e/ou colocação de cercárias em área depilada do abdômen) e intraperitoneal. Os resultados obtidos demonstraram que a via mais eficaz foi transcutânea (sub-parcial), e que a maior mortalidade ocorreu no grupo infectado por via intraperitoneal.

Trypanosomiasis cruzi: a follow-up study of tissue reacting immunoglobulins in infected purebred pinscher dogs

Antibodies against striated muscle (cardiac and skeletal) were studied in serum samples from 36 purebred prepubertal Pinscher dogs (15 Controls without infection and 21 infected with Trypanosoma cruzi from 7 to 400 days after infection with 1000 trypomastigotes/gram body weight of the Colombiana strain by the intraperitoneal route). Although three different immunohistological pattems of tissue-reacting immunoglobulins were found their presence was not correlated with any peculiar characteristics or with the severity of the disease in each particular dog.

Kinetics of the cercaria-schistosomulum transformation in vivo

Sitice most studies on the cercaria-schistosomulum transformation have been carried out in vitro, the authors used the inoculation ofcercariae into the peritoneal cavity of mice tofollow the steps involved in this progressive adaptation of cercarie to the vertebmte host. The main conclusions were: 1. Most cercariae reach the schistosomular stage between 90-120 min after intraperitoneal inoculation. 2. Changes usuallystart with detachment of the tail followed by loss, rupture or changes of the glycocalix. 3. After 120 min most larvae loss their tails and present water sensitivity. 4. Acetabular grands depletion usually does not occur in cercaria-shistosomulum changes in the peritoneal cavity of mice. These steps differ in some way from those described in the kinetics of the in vitro observations performed by other investigators, and is more like those described in the penetration in the skin of living vertebrates.

Ensaio terapêutico com glucantime em sagüis (Callithrix jacchus) infectados com uma cepa de Leishmania donovani aparentemente resistente ao tratamento

Os autores relatam o resultado de um ensaio terapêutico em sagüis com uma cepa de Leishmania donovani isolada de um caso humano fatal de calazar, clinicamente resistente aos antimoniais (Glucantime e Pentostam), Anfotericina B ePentamidina. Os testes cutâneos realizados no paciente para avaliação da imunidade celular foram negativos à exceção do DNCB a 2%. Quatro sangüis adultos (Callithrix jacchus) foram inoculados por via intraperitoneal com uma suspensão deformas amastigotas de L. donovani. Duzentos e dez dias após, todos os animais mostravam formas amastigotas do protozoário, evidenciadas através de punção hepática por aspiração. Iniciou-se então um esquema terapêutico com glucantime (28 mgSb v/kg/dia) em três séries de 10 dias com cinco dias de intervalo entre elas em três dosprimatas,ficando o quarto animal como controle. Nos três animais tratados houve curaparasitológica da doença, o mesmo não ocorrehdo com o controle. O fato de a amostra de L. donovani ter sido, no paciente, resistente aos vários tratamentos e ter sido sensível em modelo experimental à terapêutica com glucantime, sugere a possibilidade de que fatores imunológicos do paciente possam ter contribuído para a evolução fatal da doença.

Estudo parasitológico e anátomo-patológico da fase aguda da doença de Chagas em cães inoculados com duas diferentes cepas do Trypanosoma cruzi

Cães jovens foram infectados com as cepas Y e CL do T. cruzi usando-se como inóculos 107 formas sangüíneas inoculadaspor via intraperitoneal e 2 x 10³ tripomastigotas metacíclicos obtidos do inseto vetor e inoculadospor via conjuntival. As cepas Ye CL induziram nos cães curvas deparasitemia 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 lesões predominaram no miocárdio. Entretanto, com a cepa Y a miocardite foi sempre intensa desde as fases mais precoces da infecção, ao passo que com a cepa CL o processo inflamatório tomou-se acentuado somente a partir do 20.° dia. Freqüentemente a intensidade da miocardite observada em alguns animais não guardava relação com a parasitemia; em alguns cães com parasitemia subpatente, nos quais a infecção só foi diagnosticada pelo xenodiagnóstico, a intensidade da miocardite foi comparável àquela observada nos animais com parasitemia patente. Idêntica correlação também não foi assinalada em relação ao parasitismo tissular. Esses achados sugerem a participação de mecanismo imunológicos na gênese das lesões, ainda na fase aguda da infecção.

Infecção experimental de macacos cebus apella sp pelo Trypanosoma cruzi: avaliação clínica, eletrocardiqgráfica e anatomopatológica

Dos trinta e dois macacos capturados no interior do Estado de São Paulo e mantidos em laboratório em gaiolas individuais (24 a 25 C° e 70% de umidificação) após vários xenodiagnósticos negativos, 12 foram infectados por via intraperitoneal com diferentes cepas de Trypanosoma cruzi, cujas formas tripomastigotas injetadas variaram de 1.10(5) a 5.10(6) Os 20 macacos restantes foram mantidos como controle. No período de 1 a 6 anos tanto os animais inoculados como os não inoculados, foram submetidos axenodiagnóstico e teste soro lógico de aglutinação direta, exame clínico e o eletrocardiograma. Posteriormente os macacos foram necropsiados e todos os órgãos submetidos a exame macro e microscópico. O exame clínico e o eletrocardiograma não revelaram alterações. Dos 12 macacos infectados, 4 apresentaram evidências de infecção ao exame histopatológico: utn com formas amastigotas nos tecidos e 3 com miocardite crônica de grau leve. A parasitemiafoi comprovada em 66,66% dos animais na fase aguda e a sorologia em 91,66% na fase crônica. Concluiu-se que os macacos Cebus não expressaram susceptibilidade ao desenvolvimento das lesões que caracterizam a fase . crônica da doença de Chagas mas poderiam ser usados para manter as cepas de T. cruzi e estudos de pesquisa sorológico a longo termo.

The hemorrhagic syndrome of leptospirosis: an experimental study in guinea pigs

The hemorrhagic syndrome of leptospirosis was studied in guinea pigs. The study correlates hematological, histopathological and immunohistochemical alterations in sixty animals inoculated by the intraperitoneal route with lml of the culture of virulent strain of Leptospira interrogans serovar copenhageni. Leptospirae antigens were detected by immunoperoxidase, chiefly in liver, kidney and heart muscle capillaries. Possible pathogenic mechanisms responsible for hemorrhagic syndrome are discussed with emphasis on toxic and anoxic attacks causing damage to endothelia, platelet depletion and alterations to hemostasia rates: prothrombin time [FT], partial thromboplastin time [PIT] and fibrinogen concentrations. Tide clinical-laboratoiy picture is compatible with the histopathological observation of disseminated intravascular coagulation [D1C] in most of the guinea pigs from day 4 of infection.

The FML (Fucose Mannose Ligand) of Leishmania donovani: a new tool in diagnosis, prognosis, transfusional control and vaccination against human kala-azar

The Fucose-Mannose Ligand (FML) of Leishmania donovani is a complex glycoproteic fraction. Its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil. The FML-ELISA test, showed 100% sensitivity and 96% specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. More than 20% apparently healthy subjects with positive reaction to FML developed overt kala-azar during the following 10 months. In the screening of human blood donnors, a prevalence of 5% of sororeactive subjects was detected, attaining 17% in a single day. The GP36 glycoprotein of FHL is specifically reconized by human kala-azar sera. The immunoprotective effect of FML on experimental L. donovanii infection was tested in swiss albino mice. The protection scheemes included three weekly doses of FML, supplemented or not with saponin by the subcutaneous or intraperitoneal routes and challenge with 2x 10(7) amastigotes of Leishmania donovani. An enhancement of 80.0 % in antibody response (p<0.001) and reduction of 85.5 % parasite liver burden (p<0.001) was detected in animals immunized with FML saponin, unrespectivety of the immunization route.

An intermittent schedule is better than continuous regimen of antimonial therapy for cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil

This study reviews a series of cutaneous leishmaniasis cases diagnosed and treated in outpatient units in the municipality of Rio de Janeiro, where the intermittent schedule of antimonial therapy was replaced by the continuous regimen. Both schedules were based on daily intramuscular injections of pentavalent antimonial. Forty-nine subjects received the intermittent regimen, consisting of three ten-day series alternated with ten-day rest intervals whereas seventy-one patients received the continuous regimen during 20 consecutive days. The study groups had similar composition regarding age, sex and clinical condition. The cure rate was significantly higher in the group receiving the intermittent schedule than in the group receiving continuous therapy (89.8% vs 63.3%). Moreover, loss to follow-up was significantly more frequent in the group receiving continuous therapy (19.7% vs 4.1% in the intermittent therapy). Under field conditions, the intermittent regimen provided higher effectiveness and adherence than the continuous schedule.