RESUMO
A phage-display library was generated using a Bus thalamus scorpion toxin (BTK-2) as a peptide scaffold. BTK-2 belongs to the disulfide-rich family of proteins with pronounced structural stability due to the presence of three disulfide bridges that connects antiparallel beta-sheets and one alpha helix. Using BTK-2 as a phage display scaffold, we introduced mutations in five residues located in the alpha-helix and two residues located in the smaller loop, keeping intact the disulfide bridges to create a peptide phage-displayed library with disulfide-rich family properties. The library was subjected to in vivo and in vitro phage display selections against Trypanosoma evansi, the etiological agent of "Surra", a disease that affects a wide range of mammals. The development of T. evansi specific biomarkers is essential to improve diagnostic methods and epidemiological studies leading to a more accurate clinical decision for the treatment of this disease of economic impact for commercial livestock production. In this study, we identified two disulfide-rich peptides targeting T. evansi parasites. Further specificity studies are necessary to investigate the potential of selected peptides as new biomarkers to aid diagnostic and treatment procedures of T. evansi infections.
Assuntos
Dissulfetos , Peptídeos , Trypanosoma/química , Tripanossomíase/diagnóstico , Tripanossomíase/terapia , Sequência de Aminoácidos , Animais , Biomarcadores , Clonagem Molecular , Dissulfetos/química , Camundongos , Camundongos Endogâmicos BALB C , Mutagênese , Oligonucleotídeos/química , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos/genética , Venenos de Escorpião/química , Venenos de Escorpião/genéticaRESUMO
Acidocalcisomes are acidic calcium stores rich in polyphosphate and found in a diverse range of organisms. The mechanism of Ca(2+) release from these organelles was unknown. Here we present evidence that Trypanosoma brucei acidocalcisomes possess an inositol 1,4,5-trisphosphate receptor (TbIP(3)R) for Ca(2+) release. Localization studies in cell lines expressing TbIP(3)R in its endogenous locus fused to an epitope tag revealed its partial colocalization with the vacuolar proton pyrophosphatase, a marker of acidocalcisomes. IP(3) was able to stimulate Ca(2+) release from a chicken B-lymphocyte cell line in which the genes for all three vertebrate IP(3)Rs have been stably ablated (DT40-3KO) and that were stably expressing TbIP(3)R, providing evidence of its function. IP(3) was also able to release Ca(2+) from permeabilized trypanosomes or isolated acidocalcisomes and photolytic release of IP(3) in intact trypanosomes loaded with Fluo-4 elicited a transient Ca(2+) increase in their cytosol. Ablation of TbIP(3)R by RNA interference caused a significant reduction of IP(3)-mediated Ca(2+) release in trypanosomes and resulted in defects in growth in culture and infectivity in mice. Taken together, the data provide evidence of the presence of a functional IP(3)R as a Ca(2+) release channel in acidocalcisomes of trypanosomes and suggest that a Ca(2+) signaling pathway that involves acidocalcisomes is required for growth and establishment of infection.
Assuntos
Cálcio/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Organelas/metabolismo , Trypanosoma brucei brucei/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Inositol 1,4,5-Trifosfato/metabolismo , Inositol 1,4,5-Trifosfato/farmacologia , Receptores de Inositol 1,4,5-Trifosfato/genética , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Mutação , Organelas/efeitos dos fármacos , Interferência de RNA , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/crescimento & desenvolvimento , Tripanossomíase/parasitologia , Tripanossomíase/terapiaRESUMO
The effects of treatment with probiotics on the immunological and hematobiochemical changes in Trypanosoma brucei infection were investigated. Probiotic strains used are Bifidobacterium BB-12, Lactobacillus acidophilus LA-5, Lactobacillus delbrueckii LBY-27, Lactobacillus paracasei LC-01, and Streptococcus thermophilus STY-31. Thirty rats randomly assigned to five groups were used in the experiment. Groups A to C received 1 × 109 CFU, 5 × 109 CFU, and 10 × 109 CFU of the multi-strain probiotics daily and respectively from day 0 post-supplementation (PS) to termination. Group D and E were the infected and uninfected controls respectively. On day seven PS, groups A to D were challenged intraperitoneally with approximately 1 × 106 trypanosomes. Parasitemia, nitric oxide level, hematobiochemical parameters, and antibody titer to heterologous antigen stimulation were monitored post-infection. By days 7 and 16 PS, probiotics-treated groups had significantly lower (p < 0.05) mean creatinine concentration than the controls; however, on day 7 PS, there were no significant variations in the leukocyte counts (LC), total erythrocyte counts (TEC), and the packed cell volume (PCV) in all experimental groups. Following infection, by day 16 PS, the pre-patent period, parasitemia levels, and antibody titer were similar in all infected groups. Furthermore, the probiotics-treated groups and the infected control had significantly lower PCV, TEC, and LC values when compared to the uninfected control, and probiotics treated groups (A and C) had only marginally lower nitric oxide levels than the infected control. Treatment with the probiotic strains gave a creatinine-lowering effect, was innocuous to the hematopoietic system, but was not sufficiently immunostimulatory in trypanosomosis.
Assuntos
Imunidade , Probióticos/uso terapêutico , Tripanossomíase/terapia , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Almost three out of every four people in the world who suffer a fatal stroke live in developing countries. A number of different tropical diseases may appear in Europe in the coming years as a consequence of the demographic change that is being brought about by migratory flows. We review the main infectious causes of strokes in the tropics. DEVELOPMENT: There are estimated to be 500 million cases of malaria every year. Cerebral malaria can cause cerebral oedema, diffuse or focal compromise of the subcortical white matter and cortical, cerebellar and pontine infarctions. Chagas disease is an independent risk factor for stroke in South America. At least 20 million people have the chronic form of Chagas disease. The main prognostic factors for Chagas-related stroke are the presence of apical aneurysms, arrhythmia and heart failure. Vascular complications of neurocysticercosis include transient ischemic attacks, ischemic strokes due to angiitis and intracranial haemorrhages. The frequency of cerebral infarction associated with neurocysticercosis varies between 2% and 12%. Gnathostomiasis is a cause of subarachnoid haemorrhage in south-east Asia. Other less common causes of stroke are viral haemorrhagic fevers due to arenavirus and flavivirus. CONCLUSIONS: Several diseases that are endemic in the tropics can be responsible for up to 10% of the cases of strokes in adults.
Assuntos
Infecções do Sistema Nervoso Central/complicações , Acidente Vascular Cerebral/etiologia , Clima Tropical , Medicina Tropical , Animais , Infecções do Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/fisiopatologia , Infecções do Sistema Nervoso Central/terapia , Doença de Chagas/complicações , Doença de Chagas/patologia , Doença de Chagas/fisiopatologia , Doença de Chagas/terapia , Diagnóstico Diferencial , Gnathostoma/parasitologia , Febres Hemorrágicas Virais/complicações , Febres Hemorrágicas Virais/patologia , Febres Hemorrágicas Virais/fisiopatologia , Febres Hemorrágicas Virais/terapia , Humanos , Malária/complicações , Malária/patologia , Malária/fisiopatologia , Malária/terapia , Neurocisticercose/complicações , Neurocisticercose/patologia , Neurocisticercose/fisiopatologia , Neurocisticercose/terapia , Fatores de Risco , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Tripanossomíase/complicações , Tripanossomíase/patologia , Tripanossomíase/fisiopatologia , Tripanossomíase/terapiaRESUMO
Trypanosoma evansi and T. equiperdum were compared regarding their ultrastructure, their mammalian hosts, way of transmission, pathogenicity, diagnosis and treatment, and biochemical and molecular characteristics. Electron microscopic investigation revealed no ultrastructural differences between the two species except that there were more coated vesicles in the flagellar pocket of T. equiperdum. Biological, biochemical and molecular studies were reviewed and exhibited many similarities between T. evansi and T. equiperdum. The most prominent differences between the two species are the presence of maxicircles in T. equiperdum, which are missing in T. evansi, and the route of transmission. While T. evansi is transmitted by biting flies, T. equiperdum is transmitted from one equine host to another during copulation when mucous membranes come into contact. Otherwise the two species are remarkably similar. The phylogenetic relationship between the two species and T. b. brucei is being discussed, and the hypothesis is proposed that T. evansi arose from a clone of T. equiperdum which lost its maxicircles.
Assuntos
Doenças dos Bovinos/parasitologia , Doenças dos Cavalos/parasitologia , Trypanosoma/classificação , Tripanossomíase/veterinária , Animais , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/terapia , Feminino , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Cavalos , Interações Hospedeiro-Parasita , Isoenzimas/análise , Masculino , Camundongos , Microscopia Eletrônica/veterinária , Filogenia , Trypanosoma/patogenicidade , Trypanosoma/ultraestrutura , Tripanossomíase/diagnóstico , Tripanossomíase/parasitologia , Tripanossomíase/terapiaRESUMO
Sialidase activity identical to 0.0196 mg per ml of liberated sialic acids (2.11 Units) was detected in small intestinal contents of goats. Mg++ and Ca++ induced in vitro detection in mucosa cells of both small and large intestines. Magnesium alone induced sialidase activities identical to 0.0128 mg per ml of liberated sialic acids (1.38 Units) and 0.0166 mg per ml (1.79 Units) in small and large intestinal mucosal cells, respectively. Mg++ and Ca++ together induced higher sialidase activities identical to 0.0191 mg per ml (2.06 Units) and 0.0194 mg per ml (2.09 Units) in small and large intestinal mucosal cells, respectively. The enzyme activity was slightly higher in large than in small intestinal mucosal cells. The results are discussed in relation to control of African animal trypanosomiasis.
Assuntos
Cálcio/farmacologia , Cabras/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Magnésio/farmacologia , Neuraminidase/metabolismo , Animais , Técnicas In Vitro , Mucosa Intestinal/enzimologia , Ácidos Siálicos/análise , Tripanossomíase/terapiaRESUMO
Abstract Trypanosomiasis caused by Trypanosoma evansi can seriously affect both domestic and wild animals. This article reports on an outbreak of canine trypanosomiasis on a farm in the Pantanal region of Brazil. The farm had 38 dogs, 20 of which died before receiving veterinary care. The remaining 18 dogs were underwent anamnesisn, clinical examination, hematological and biochemical evaluations. Blood smears and PCR analysis were performed for the diagnosis. The treatment protocols used according to the clinical recovery or parasitological cure of the dogs, using diminazene diaceturate, isometamidium chloride or quinapyramine sulfate. Post-treatment parasitological evaluation was performed by the microhematocrit technique. 7/18 dogs were PCR positive for T. evansi (confirmed by sequencing). There was clinical findings, which were consistent with both the acute and chronic stages of the disease in dogs. The infected dogs all exhibited at least one clinical sign of the disease. The hematological findings were compatible with trypanosomiasis, highlighting the hypochromic microcytic anemia as the main outcome. No treatment protocol was fully effective and the prolonged use of diminazene diaceturate caused the death of an animal. The trypanosomiasis can cause high rates of morbidity and mortality in dogs and difficulty in establishment an effective and safe therapeutic protocol.
Resumo A tripanossomíase causada por Trypanosoma evansi pode acometer gravemente os animais domésticos e selvagens. Este artigo relata um surto de tripanossomíase canina em uma fazenda na região do Pantanal, Brasil. Na fazenda havia 38 cães, 20 dos quais morreram antes de receber cuidados veterinários. Os 18 cães restantes foram submetidos a anamnese, exame clínico, avaliação hematológica e bioquímica. Esfregaços de sangue e análise da PCR foram realizados para o diagnóstico. Os protocolos de tratamento foram utilizados de acordo com a recuperação clínica ou cura parasitológica dos cães, utilizando diaceturato de diminazeno, cloreto de isometamídio ou sulfato de quinapiramina. A avaliação parasitológica pós-tratamento foi realizada pela técnica de microhematócrito. 7/18 cães foram PCR positivos para T. evansi (confirmado por sequenciamento). Os achados clínicos encontrados, foram consistentes com os estágios agudo e crônico da doença em cães. Todos os cães infectados exibiram pelo menos um sinal clínico da doença. Os achados hematológicos foram compatíveis com a tripanossomíase, destacando a anemia microcítica hipocrômica como principal consequência. Nenhum protocolo de tratamento foi totalmente eficaz e o uso prolongado de diaceturato de diminazeno causou a morte de um animal. A tripanossomíase pode causar altas taxas de morbidade e mortalidade em cães e dificultar o estabelecimento de um protocolo terapêutico eficaz e seguro.
Assuntos
Humanos , Masculino , Feminino , Cães , Fenantridinas/uso terapêutico , Compostos de Quinolínio/uso terapêutico , Tripanossomíase/diagnóstico , Diminazena/análogos & derivados , Doenças do Cão/diagnóstico , Tripanossomíase/terapia , Tripanossomíase/epidemiologia , Brasil/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Surtos de Doenças , Diminazena/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologiaRESUMO
Trypanosomes are protozoan parasites that cause diseases in humans and livestock for which no vaccines are available. Disease eradication requires sensitive diagnostic tools and efficient treatment strategies. Immunodiagnostics based on antigen detection are preferable to antibody detection because the latter cannot differentiate between active infection and cure. Classical monoclonal antibodies are inaccessible to cryptic epitopes (based on their size-150 kDa), costly to produce and require cold chain maintenance, a condition that is difficult to achieve in trypanosomiasis endemic regions, which are mostly rural. Nanobodies are recombinant, heat-stable, small-sized (15 kDa), antigen-specific, single-domain, variable fragments derived from heavy chain-only antibodies in camelids. Because of numerous advantages over classical antibodies, we investigated the use of nanobodies for the targeting of trypanosome-specific antigens and diagnostic potential. An alpaca was immunized using lysates of Trypanosoma evansi. Using phage display and bio-panning techniques, a cross-reactive nanobody (Nb392) targeting all trypanosome species and isolates tested was selected. Imunoblotting, immunofluorescence microscopy, immunoprecipitation and mass spectrometry assays were combined to identify the target recognized. Nb392 targets paraflagellar rod protein (PFR1) of T. evansi, T. brucei, T. congolense and T. vivax. Two different RNAi mutants with defective PFR assembly (PFR2RNAi and KIF9BRNAi) were used to confirm its specificity. In conclusion, using a complex protein mixture for alpaca immunization, we generated a highly specific nanobody (Nb392) that targets a conserved trypanosome protein, i.e., PFR1 in the flagella of trypanosomes. Nb392 is an excellent marker for the PFR and can be useful in the diagnosis of trypanosomiasis. In addition, as demonstrated, Nb392 can be a useful research or PFR protein isolation tool.
Assuntos
Antígenos de Protozoários/imunologia , Proteínas de Protozoários/imunologia , Anticorpos de Cadeia Única/uso terapêutico , Tripanossomicidas/uso terapêutico , Tripanossomíase/prevenção & controle , Sequência de Aminoácidos , Animais , Camelídeos Americanos , Flagelos/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Pesadas de Imunoglobulinas/uso terapêutico , Dados de Sequência Molecular , Interferência de RNA , RNA Interferente Pequeno , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Alinhamento de Sequência , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Tripanossomicidas/imunologia , Trypanosoma/imunologia , Tripanossomíase/terapiaAssuntos
Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Trypanosoma/classificação , Tripanossomíase/diagnóstico , Adulto , Animais , Biópsia por Agulha , Infecções Protozoárias do Sistema Nervoso Central/patologia , Infecções Protozoárias do Sistema Nervoso Central/terapia , Craniotomia , Progressão da Doença , Evolução Fatal , Humanos , Imuno-Histoquímica , Masculino , Manitoba , Nitroimidazóis/uso terapêutico , Prisioneiros , Tomografia Computadorizada por Raios X , Tripanossomíase/terapiaRESUMO
A 9-year-old male Jack Russell Terrier with a history of travel to Thailand was presented with chronic lethargy, weight loss, unilateral anterior uveitis, pancytopenia, hyperglobulinemia, and proteinuria. Numerous trypomastigotes were found on a blood smear, and using molecular methods the parasite was identified as Trypanosoma evansi. After initial response to treatment, the dog experienced a relapse with central neurologic signs 88 days after initial presentation and died. Antibodies to T evansi were detected in both serum and cerebrospinal fluid (CSF) using a card agglutination test (CATT/T evansi), and PCR analysis of CSF for T evansi was positive. Findings at necropsy included marked non-purulent meningoencephalitis. Chronic infection with T evansi in a dog that returned to Germany following international travel highlights the risk associated with introduction of foreign animal diseases to Europe and the possibility of these infections becoming endemic. Detection of chronic infection and curative therapy of trypanosomiasis are challenging, and infection is usually fatal in the dog.
Assuntos
Anticorpos Antiprotozoários/líquido cefalorraquidiano , Antígenos de Protozoários/imunologia , Doenças do Cão/diagnóstico , Trypanosoma/imunologia , Tripanossomíase/veterinária , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Antiprotozoários/sangue , Transfusão de Sangue , Carbazóis/uso terapêutico , Doenças do Cão/parasitologia , Doenças do Cão/terapia , Cães , Quimioterapia Combinada , Evolução Fatal , Alemanha , Masculino , Pancitopenia/diagnóstico , Pancitopenia/terapia , Pancitopenia/veterinária , Suramina/uso terapêutico , Tailândia , Viagem , Tripanossomicidas/uso terapêutico , Trypanosoma/genética , Trypanosoma/isolamento & purificação , Tripanossomíase/diagnóstico , Tripanossomíase/parasitologia , Tripanossomíase/terapia , Uveíte/diagnóstico , Uveíte/parasitologia , Uveíte/terapia , Uveíte/veterináriaRESUMO
Around 1900 Laveran and Mesnil discovered that African trypanosomes do not survive in the blood of some primates and humans. The nature of the trypanolytic factor present in these sera has been the focus of a long-standing debate between different groups. The aim of this study was to investigate the susceptibility of T. evansi isolates to therapy using human blood and plasma in experimentally infected mice. Forty-eight 2-month-old female mice (Mus musculus) were divided into six groups of eight animals per group (A, B, C, D, E and F). Plasma was obtained after blood collection in order to perform therapy. Animals from group A (positive control) were inoculated with T. evansi and treated with 0.2mL of saline solution. Animals from groups B and C were infected with the flagellate and received a curative treatment with 0.2mL of human blood (group B) and 0.2mL of human plasma (group C), 24h after infection. Animals from groups D and E received a prophylactic treatment with 0.2mL of human blood and 0.2mL of human plasma, respectively, 24h prior to the infection. Animals from group F (negative control) were not infected and received 0.2mL of saline solution. The four treatments (B, C, D and E) increased animals longevity when compared to group A. Prepatency period was longer in groups D (15 days) and E (37.7 days) under prophylactic immunotherapy. Moreover, no parasites were found in most of the animals 60 days post-inoculation (PI). Besides the longer longevity, treatments were capable of curing 50% of mice of group B, 37.5% of group C, 37.5% of group D and 25% of the animals from group E.
Assuntos
Sangue , Plasma , Trypanosoma/fisiologia , Tripanossomíase/parasitologia , Tripanossomíase/terapia , Animais , Sangue/parasitologia , Feminino , Humanos , Camundongos , Análise de Sobrevida , Tripanossomicidas/administração & dosagem , Tripanossomíase/mortalidadeAssuntos
Infecções por Protozoários/prevenção & controle , Infecções por Protozoários/terapia , Criptosporidiose/imunologia , Criptosporidiose/prevenção & controle , Criptosporidiose/terapia , Equinococose/imunologia , Equinococose/prevenção & controle , Equinococose/terapia , Humanos , Imunoterapia , Leishmaniose/imunologia , Leishmaniose/prevenção & controle , Leishmaniose/terapia , Malária/imunologia , Malária/prevenção & controle , Malária/terapia , Infecções por Protozoários/imunologia , Esquistossomose/imunologia , Esquistossomose/prevenção & controle , Esquistossomose/terapia , Toxoplasmose/imunologia , Toxoplasmose/prevenção & controle , Toxoplasmose/terapia , Triquinelose/imunologia , Triquinelose/prevenção & controle , Triquinelose/terapia , Tripanossomíase/imunologia , Tripanossomíase/prevenção & controle , Tripanossomíase/terapiaAssuntos
Trypanosoma/patogenicidade , Tripanossomíase/terapia , Animais , Temperatura Alta , CamundongosRESUMO
Chagas' disease is an important health problem in most Latin American countries, and a concern in dog populations, which act as a reservoir. We showed in previous studies that a therapeutic DNA vaccine could partially control the pathology after Trypanosoma cruzi infection in mice, and this vaccine may represent an alternative treatment for Chagas' disease. Here we evaluated the therapeutic efficacy of this vaccine in experimentally infected dogs for up to 2 months after infection. Our results suggest that DNA vaccine treatment may affect the immune response and delay Chagas' disease progression in T. cruzi-infected dogs, and confirm the potential of this novel treatment.
Assuntos
Trypanosoma cruzi/patogenicidade , Tripanossomíase/veterinária , Vacinas de DNA/uso terapêutico , Animais , Cães , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Tripanossomíase/parasitologia , Tripanossomíase/fisiopatologia , Tripanossomíase/terapiaRESUMO
Passive transfer of plasma from a mouse cured of parasitemia to a Trypanosoma musculi-infected host rapidly eliminates parasitemia; this curative activity, presumably mediated by an immunoglobulin, is sensitive to heat treatment (56 degrees C, 30 min). In addition, pretreatment with immune plasma, even after heat treatment, prevents the development of a patent parasitemia in a naive host (protective activity).
Assuntos
Temperatura Alta , Soros Imunes , Tripanossomíase/terapia , Animais , Imunização Passiva , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
This study investigated the effect of splenectomy on the production of ablastin and the elimination of Trypanosoma lewisi from the circulation of infected Porton rats. Rats were splenectomized or sham-splenectomized either before or at various stages during the infection and the course of the parasitaemia compared with untreated control animals. Ablastin titres in the serum were measured by a sensitive in vitro assay and were found to be the same in all the rats, regardless of the nature or timing of the operation. Splenectomized animals eliminated the parasite more slowly from the circulation than either the sham-splenectomized animals or unoperated controls. It is concluded that the presence of the spleen enables the rat to clear the parasite more rapidly from the circulation, but that the spleen is not essential for the production ablastin during the infection.
Assuntos
Imunoglobulina G/biossíntese , Esplenectomia , Tripanossomíase/parasitologia , Animais , Formação de Anticorpos , Imunoglobulina G/fisiologia , Masculino , Ratos , Ratos Endogâmicos , Trypanosoma lewisi/imunologia , Tripanossomíase/imunologia , Tripanossomíase/terapiaRESUMO
The trypanosomes multiply during prepatency after minimal infection by a factor of 2.2-3.6 per day. During patency, increase of trypanosome number in the peripheral blood is basically non-logarithmic as the actual proliferating forms remain hidden in special vascular areas (kidney, placenta). The mean increase during patency is approximately linear, typically by 1-10 trypanosomes per 10(4) erythrocytes per day, and depends on the number of infective organisms introduced. - Length of parasitemia is 13-40 days, it is partly determined genetically. Prolonged parasitemias, very low in the later stages, were seen in mice preinfected with Trypanosoma congolense. - In 1 mouse with minimal infection, parasitemia only became patent 63 days after infection under the stress of an added infection with Trypanosoma brucei. - Parasitemia can be terminated by antiserum. Application of antiserum 3 or 4 days after infection may even suppress the development of immunity and priming. - Massive reinfection leads to parasitemia of up to 8 days duration without parasite multiplication.
Assuntos
Trypanosoma/crescimento & desenvolvimento , Tripanossomíase/parasitologia , Animais , Feminino , Imunização Passiva , Camundongos , Camundongos Endogâmicos , Gravidez , Complicações Infecciosas na Gravidez/parasitologia , Trypanosoma brucei brucei , Tripanossomíase/genética , Tripanossomíase/terapiaRESUMO
The ability of immune plasma (IP) taken from different donor strains of mice to cure Trypanosoma musculi infection in various recipient mouse strains, when given during the plateau phase of infection, was examined. C57BL/6, B10.A/SgSn, B10.D2/oSn, B10.D2/nSn, DBA/2, and BALB/c strains could be cured of parasitemia (giving 0.4 to 0.8 ml of IP per mouse), whereas A/J and C3H/HeN strains could not (giving up to 1.2 ml of IP per mouse). Noncure appeared to be associated with the high-plateau parasitemias (approximately 10(8] that developed in the latter strains since IP administered early in infection, when the parasite burden was similar to the plateau parasitemias (approximately 10(6] of strains that could be cured, was at least partially effective in A/J and C3H/HeN mice. The IP of any strain tested (C57BL/6, B10.D2/oSn, B10.D2/nSn, DBA/2, A/J, or C3H/HeN) could bring about elimination of trypanosomes in strains able to be cured. The potency of IP from different strains varied, being greater in the strains that developed higher-plateau parasitemias. Potency of IP appears to correlate positively with the titers of trypanosome-specific antibody of the immunoglobulin G2a isotype (the curative antibody). The role of the late-acting complement components was examined. In C5-deficient mice the course of infection was normal, although the elimination phase was delayed by a few days. Cure of parasitemia by IP administered during the plateau phase was equally effective in the presence or absence of C5 in either the donor or the recipient. When tested in vitro, however, IP only exhibited antitrypanosomal activity when added to infected blood taken from C5-sufficient strains of mice. We conclude that in vitro, under the conditions used in the assay, antibody-mediated destruction of the trypanosomes is brought about by complement-mediated lysis. This process, although it probably occurs to some extent, is unlikely to be the major mechanism of trypanosome elimination in vivo.
Assuntos
Anticorpos Antiprotozoários/uso terapêutico , Tripanossomíase/terapia , Animais , Especificidade de Anticorpos , Complemento C5/fisiologia , Feminino , Imunoglobulina G , Masculino , Camundongos , Camundongos Endogâmicos A , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Plasma/imunologia , Especificidade da Espécie , Trypanosoma/imunologia , Tripanossomíase/imunologia , Tripanossomíase/parasitologiaRESUMO
The last successfully treated case of congenital trypanosomiasis in Zambia was in October 1978, with detailed analysis of immunoglobulins, illustrating the waning of blood and serum levels of IgA, IgG, and IgM during treatment, up to 99 days after treatment. Twenty-five years later, we report on a case of congenital trypanosomiasis. The disease is now rare and can be missed or dismissed as retroviral disease, particularly in adults. The main unusual symptoms were the prolonged intermittent convulsions in an otherwise well infant. Management of the disease is now more interdisciplinary, resources for laboratory support are fewer, lumbar puncture is more relevant, and antitrypanosomal drugs are more difficult to obtain. The mother died within one week of hospitalization and the infant initially responded to three doses of suramin and 3 weeks of melsopropol. Convulsions ceased during the second round of melsopropol. Unfortunately, the infant died of nosocomial infection.
Assuntos
Transmissão Vertical de Doenças Infecciosas , Complicações Parasitárias na Gravidez/diagnóstico , Tripanossomíase/congênito , Tripanossomíase/diagnóstico , Adulto , Países em Desenvolvimento , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Lactente , Gravidez , Medição de Risco , Índice de Gravidade de Doença , Tripanossomicidas/uso terapêutico , Tripanossomíase/terapia , ZâmbiaRESUMO
The cure of Trypanosoma equiperdum infected Mice obtained after treatment with an association of electromagnetic waves and a magnetic field is probably linked with the immune state of the host. A severe depression of the immune system suppresses the ability of the animals to eliminate the parasites after physical stimulation.