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1.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33625354

RESUMO

Introduction. Cryptosporidium parvum causes intestinal parasitic infections affecting both immunosuppressed and immunocompetent individuals.Gap statement. Given the absence of effective treatments for cryptosporidiosis, especially in immunodeficient patients, the present study was designed to assess the therapeutic efficacy of secnidazole (SEC) and its combination with nitazoxanide (NTZ) in comparison to single NTZ treatment in relation to the immune status of a murine model of C. parvum infection.Methodology. The infected groups were administered NTZ, SEC or NTZ-SEC for three or five successive doses. At days 10 and 12 post-infection (p.i.), the mice were sacrificed, and the efficacy of the applied drugs was evaluated by comparing the histopathological alterations in ileum and measuring the T helper Th1 (interferon gamma; IFN-γ), Th2 [interleukin (IL)-4 and IL-10] and Th17 (IL-17) cytokine profiles in serum.Results. The NTZ-SEC combination recorded the maximal reduction of C. parvum oocyst shedding, endogenous stages count and intestinal histopathology, regardless of the immune status of the infected mice. The efficacy of NTZ-SEC was dependent on the period of administration, as the 5 day-based treatment protocol was also more effective than the 3 day-based one in terms of immunocompetence and immunosuppression. The present treatment schedule induced an immunomodulatory effect from SEC that developed a protective immune response against C. parvum infection with reduced production of serum IL-17, IFN-γ, IL-4 and IL-10.Conclusions. Application of NTZ-SEC combined therapy may be useful in treatment of C. parvum, especially in cases involving immunosuppression.


Assuntos
Antiprotozoários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Metronidazol/análogos & derivados , Nitrocompostos/uso terapêutico , Tiazóis/uso terapêutico , Animais , Criptosporidiose/imunologia , Criptosporidiose/parasitologia , Criptosporidiose/patologia , Cryptosporidium parvum/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Esquema de Medicação , Quimioterapia Combinada , Íleo/efeitos dos fármacos , Íleo/parasitologia , Íleo/patologia , Hospedeiro Imunocomprometido , Masculino , Metronidazol/uso terapêutico , Camundongos , Carga Parasitária
2.
PLoS Negl Trop Dis ; 14(12): e0008947, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33338041

RESUMO

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be considered for further studies in human leishmaniases. Further clinical trials are needed to confirm these findings, to determine if there are relapses after treatment and if dogs remain infective to sandflies, to define the ideal therapeutic dosage and duration of treatment with artesunate.


Assuntos
Alopurinol/uso terapêutico , Antiprotozoários/uso terapêutico , Artesunato/uso terapêutico , Doenças do Cão/tratamento farmacológico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Antimoniato de Meglumina/uso terapêutico , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Masculino , Carga Parasitária/veterinária , Parasitemia/tratamento farmacológico , Zoonoses
3.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 409-413, 2020 Aug 22.
Artigo em Chinês | MEDLINE | ID: mdl-32935519

RESUMO

OBJECTIVE: To evaluate the association between blood test parameters and intensity of Plasmodium falciparum infections among imported falciparum malaria cases in Tianjin City from 2015 to 2019, so as to provide insights into the early diagnosis of imported P. falciparum malaria. METHODS: The epidemiological data of 37 imported cases with confirmed diagnosis of P. falciparum malaria in Tianjin City from 2015 to 2019 were collected, and the epidemiological features and clinical manifestations were retrospectively analyzed. In addition, the association between blood test parameters and intensity of P. falciparum infections was evaluated among the imported P. falciparum malaria cases. RESULTS: Among the 31 imported P. falciparum malaria cases, there were 31 cases (83.8%) with a reduction in platelet (PLT) counts, 16 cases (43.2%) with a reduction in red blood cell (RBC) counts, 16 cases (43.2%) with a reduction in hemoglobin (Hb) concentrations, 23 cases (62.2%) with a rise in neutrophil percentage (NEUT%), 32 cases (86.5%) with a rise in total bilirubin (TBIL) concentrations, 29 cases (78.4%) with a rise in alanine aminotransferase (ALT) concentrations, 28 cases (75.7%) with a rise in aspartate transaminase (AST) concentrations, and 23 cases (62.2%) with a rise in gamma-glutamyl transpetidase (GGT) concentrations. The PLT count and Hb concentration correlated negatively with the intensity of P. falciparum infections (Goodman-Kruskal γ = -0.568 and -0.521, both P values < 0.05) and the TBIL concentration and NEUT% correlated positively with the intensity of P. falciparum infections (Goodman-Kruskal γ = 0.496 and 0.610, both P values < 0.05) among imported falciparum malaria cases; however, there were no associations of ALT, AST, GGT levels or RBC count with the intensity of P. falciparum infections among the imported falciparum malaria cases (Goodman-Kruskal γ = 0.370, 0.497, 0.314 and -0.434, all P values > 0.05). CONCLUSIONS: PLT, Hb, TBIL and NEUT% may serve as markers for early auxiliary diagnosis of imported P. falciparum malaria, and PLT and TBIL may provide valuable information for the diagnosis of severe imported P. falciparum malaria.


Assuntos
Testes Hematológicos , Malária Falciparum , Carga Parasitária , China , Cidades/estatística & dados numéricos , Testes Hematológicos/estatística & dados numéricos , Humanos , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Carga Parasitária/estatística & dados numéricos , Plasmodium falciparum/fisiologia , Estudos Retrospectivos
4.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 426-427, 2020 Apr 07.
Artigo em Chinês | MEDLINE | ID: mdl-32935523

RESUMO

OBJECTIVE: To understand the situation of Anisakis infection of in market-available marine fish in Dongtai City, so as to provide the evidence for the assessment of the risk of human Anisakis infections. METHODS: Raw and fresh marine fish caught in the sea of Dongtai City for sale were collected in 2018. The fish were weighted and dissected for the identification of Anisakis, and the prevalence and intensity of Anisakis infections were calculated. In addition, the correlation between the weight of Anisakis-infected marine fish and the infection intensity of Anisakis was examined. RESULTS: There were four species of marine fish infected with Anisakis, including Trichiurus haumela, Scomberomorus niphonius, Pneumatophorus japonicus and Larimichthys polyactis. Among the 149 fish samples, there were 78 with Anisakis infections, with a prevalence rate of 52.35%. The prevalence of Anisakis infection was 100.00% (28/28), 30.00% (9/30), 0 (0/30), 53.33% (16/30) and 80.65% (25/31) in T. haumela, S. niphonius, cuttle fish, P. japonicus and L. polyactis, respectively. A total of 1 049 Anisakis worms were collected, and the overall intensity of infection was 13.45 worms per fish. Spearman correlation analysis showed a positive correlation between the weight of T. haumela and the intensity of Anisakis infection (rs = 0.38, P = 0.047), and no correlation was found in other fish species. CONCLUSIONS: There is a high rate of Anisakis infection in marine fish along the offshore areas of Dongtai City. Intensification of health education is required and healthy and safe dietary habits are encouranged.


Assuntos
Anisaquíase , Anisakis , Doenças dos Peixes , Peixes , Parasitologia de Alimentos , Animais , Anisaquíase/epidemiologia , Anisakis/fisiologia , Organismos Aquáticos/parasitologia , Peso Corporal , Doenças dos Peixes/epidemiologia , Doenças dos Peixes/parasitologia , Peixes/parasitologia , Parasitologia de Alimentos/estatística & dados numéricos , Carga Parasitária/estatística & dados numéricos
5.
PLoS Negl Trop Dis ; 14(9): e0008608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925918

RESUMO

The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/- compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/- compared to BALB/c in 5 out of 6 strains. However, Slamf1-/-macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease.


Assuntos
Macrófagos/parasitologia , Espécies Reativas de Oxigênio/metabolismo , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Trypanosoma cruzi/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Doença de Chagas/imunologia , Chlorocebus aethiops , Células Dendríticas/imunologia , Suscetibilidade a Doenças/imunologia , Células HEK293 , Coração/parasitologia , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Miocárdio/patologia , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Carga Parasitária , Células Vero
6.
Parasitol Res ; 119(10): 3541-3548, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32803333

RESUMO

The aim of this study was to evaluate, through qPCR, the prevalence of parasitemia in sick kennel dogs naturally infected by canine leishmaniasis. An evaluation of daily changes of the parasitic load in peripheral blood was also performed. A comprehensive clinical examination and the collection of several samples (blood, lymph node, skin, and conjunctiva) were performed in 140 dogs living in an endemic area. Among these, only the dogs with clinically evident leishmaniasis were enrolled (39/140; 27.9%). Twelve (30.8%) out of 39 showed parasitemia, with a low load (median: 4 Leishmania/ml) despite a high lymph node parasite load (median: 4000 Leishmania/ml) and high IFAT titers (≥ 1:640). Seven sick dogs were sampled every 4 h for 6 times during a 24-h period, in order to obtain light- and dark-span samples. Only one (14.3%) out of the seven serial sampled dogs showed Leishmania DNA in the peripheral blood in two samples (2/42; 4.8%). Surprisingly, Leishmania DNA was also detected in the peripheral blood of asymptomatic dogs, negative to both serology and PCR performed on samples other than blood (6/101; 5.9%). The present study confirms that in canine leishmaniasis parasitemia is uncommon and even transitory. Even if recommended, microscopic examination is confirmed as a low sensitivity method with a lower diagnostic utility in canine leishmaniasis than qPCR. Moreover, circulating Leishmania DNA can be found even in healthy dogs. This finding is important in clinical practice because in endemic areas it suggests a transfusion risk and a possible transmission to the vector.


Assuntos
Doenças do Cão/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Parasitemia/veterinária , Animais , DNA de Protozoário/sangue , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Cães , Leishmania infantum/genética , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Carga Parasitária/veterinária , Parasitemia/epidemiologia , Parasitemia/parasitologia , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterinária
7.
Parasitol Res ; 119(9): 3041-3051, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32779021

RESUMO

Our objective was to investigate clinical progression, presence of parasites and DNAs, parasite loads, and histological alterations in BALB/c mice and Syrian golden hamsters after intraperitoneal inoculation with Leishmania (Mundinia) martiniquensis promastigotes with a goal to choosing an appropriate animal model for visceral leishmaniasis. Infections were monitored for 16 weeks. Infected BALB/c mice were asymptomatic during the infection course. Parasite DNAs were detected in the liver at week 8 of infection, followed by clearance in most animals at week 16; whereas in the spleen, parasite DNAs were detected until week 16. These results are correlated to those obtained measuring parasite loads in both organs. No parasite DNA and no alteration in the bone marrow were observed indicating that no dissemination occurred. These results suggest the control of visceralization of L. martiniquensis by BALB/c mice. In hamsters, weight loss, cachexia, and fatigue were observed after week 11. Leishmania martiniquensis parasites were observed in tissue smears of the liver, spleen, and bone marrow by week 16. Parasite loads correlated with those from the presence of parasites and DNAs in the examined tissues. Alterations in the liver with nuclear destruction and cytoplasmic degeneration of infected hepatocytes, presence of inflammatory infiltrates, necrosis of hepatocytes, and changes in splenic architecture and reduction and deformation of white pulp in the spleen were noted. These results indicate a chronic form of visceral leishmaniasis indicating that the hamster is a suitable animal model for the study of pathological features of chronic visceral leishmaniasis caused by L. martiniquensis.


Assuntos
Leishmania/fisiologia , Leishmaniose Visceral/parasitologia , Animais , Cricetinae , Modelos Animais de Doenças , Humanos , Leishmania/genética , Fígado/parasitologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Baço/parasitologia
8.
Rev. cuba. med. trop ; 72(2): e494, mayo.-ago. 2020. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1149915

RESUMO

Objetivo. Comparar tres métodos de concentración de enteroparásitos en muestras fecales humanas. Métodos. Se diseñó un estudio transversal en el que se evaluaron 154 muestras fecales categorizadas en dos grupos: parasitados (n= 127) y no parasitados (n= 27). Las muestras fueron sometidas a tres métodos: parasitológico directo, sedimentación simple y Ritchie modificado, y a la observación microscópica en lugol y suero fisiológico a un aumento de 40X. Resultados. Se observó mayor frecuencia en la presencia de estructuras parasitarias por el método de Ritchie modificado (37 por ciento), seguido de la sedimentación simple (14,8 por ciento) en el grupo de no parasitados; mientras que en el grupo de parasitados, se observó mayor carga parasitaria obtenida por el método de Ritchie (3+ (15,8 por ciento) y 2+ (23,6 por ciento), que en la sedimentación simple (3+ (10,2 por ciento) y 2+ (22,8 por ciento). Las especies parasitarias con mayor frecuencia fueron Entamoeba coli (20,3 por ciento), Giardia lamblia (18,8 por ciento), Blastocystis hominis (15,9 por ciento) y Endomlimax nana (15,2 por ciento); además, se presentó 48,7 por ciento casos con poliparasitismo. El área bajo la curva (AUC) para los métodos de Ritchie modificado, sedimentación simple y parasitológico directo fue de 0,870; 0.648 y 0,796, respectivamente. El AUC del método de Ritchie modificado fue mayor en los varones (0,933) que en las mujeres (0.,92); así como en aquellos menores de 12 años (0,867), comparados con personas entre 12-37 años (0,833) y 18-39 años (0,800). Conclusiones. El método de Ritchie modificado presenta alto rendimiento diagnóstico y permite concentrar mayor cantidad de parásitos intestinales que el método de sedimentación simple. Además, presenta la ventaja de utilizar insumos de fácil acceso y baja toxicidad, lo que genera mayor posibilidad de implementación en los laboratorios de parasitología(AU)


Objective: Compare three enteroparasite concentration methods in human stool samples. Methods: A cross-sectional study was conducted of 154 stool samples divided into two groups: with parasites (n= 127) and without parasites (n= 27). The samples were subjected to three methods: direct parasitological examination, simple sedimentation and modified Ritchie's, and to microscopic observation in lugol and saline solution to a 40x increase. Results: In the non-parasite group the highest frequency in the presence of parasite structures was observed with the modified Ritchie's method (37 percent), followed by simple sedimentation (14.8 percent). In the parasite group a greater parasite load was obtained by Ritchie's method (3+ (15.8 percent) and 2+ (23.6 percent) than by simple sedimentation (3+ (10.2 percent) and 2+ (22.8 percent). The parasite species showing the highest frequency were Entamoeba coli (20.3 percent), Giardia lamblia (18.8 percent), Blastocystis hominis (15.9 percent) and Endomlimax nana (15.2 percent), whereas polyparasitism was found in 48.7 percent of the cases. The area under the curve (AUC) for the modified Ritchie's method, simple sedimentation technique and direct parasitological examination was 0.870, 0.648 and 0.796, respectively. In the modified Ritchie's method the AUC was greater in male (0.933) than in female subjects (0.92), as well as in subjects aged under 12 years (0.867) in comparison with people aged 12-37 years (0.833) and 18-39 years (0.800). Conclusions: The modified Ritchie's method has a high diagnostic yield and makes it possible to concentrate a larger number of intestinal parasites than the simple sedimentation method. Additionally, it has the advantage of using inputs of easy access and low toxicity, broadening the possibility of its implementation in parasitology laboratories(AU)


Assuntos
Humanos , Parasitos/parasitologia , Fezes/parasitologia , Carga Parasitária/métodos , Estudos Transversais
9.
Parasitol Res ; 119(10): 3535-3539, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681193

RESUMO

Parasites co-infecting hosts can interact directly and indirectly to affect parasite growth and disease manifestation. We examined potential interactions between two common parasites of house finches: the bacterium Mycoplasma gallisepticum that causes conjunctivitis and the intestinal coccidian parasite Isospora sp. We quantified coccidia burdens prior to and following experimental infection with M. gallisepticum, exploiting the birds' range of natural coccidia burdens. Birds with greater baseline coccidia burdens developed higher M. gallisepticum loads and longer lasting conjunctivitis following inoculation. However, experimental inoculation with M. gallisepticum did not appear to alter coccidia shedding. Our study suggests that differences in immunocompetence or condition may predispose some finches to more severe infections with both pathogens.


Assuntos
Doenças das Aves/patologia , Tentilhões , Isospora/fisiologia , Infecções por Mycoplasma/veterinária , Mycoplasma gallisepticum/fisiologia , Carga Parasitária/veterinária , Animais , Doenças das Aves/microbiologia , Doenças das Aves/parasitologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/patologia , Coinfecção/veterinária , Conjuntivite Bacteriana/microbiologia , Conjuntivite Bacteriana/parasitologia , Conjuntivite Bacteriana/patologia , Conjuntivite Bacteriana/veterinária , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/parasitologia , Suscetibilidade a Doenças/veterinária , Tentilhões/microbiologia , Tentilhões/parasitologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/parasitologia , Infecções por Mycoplasma/patologia
10.
Parasitol Res ; 119(8): 2609-2622, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535734

RESUMO

The treatment against visceral leishmaniasis (VL) presents problems, mainly related to the toxicity and/or high cost of the drugs. In this context, a prophylactic vaccination is urgently required. In the present study, a Leishmania protein called LiHyE, which was suggested recently as an antigenic marker for canine and human VL, was evaluated regarding its immunogenicity and protective efficacy in BALB/c mice against Leishmania infantum infection. In addition, the protein was used to stimulate peripheral blood mononuclear cells (PBMCs) from VL patients before and after treatment, as well as from healthy subjects. Vaccination results showed that the recombinant (rLiHyE) protein associated with liposome or saponin induced effective protection in the mice, since significant reductions in the parasite load in spleen, liver, draining lymph nodes, and bone marrow were found. The parasitological protection was associated with Th1-type cell response, since high IFN-γ, IL-12, and GM-CSF levels, in addition to low IL-4 and IL-10 production, were found. Liposome induced a better parasitological and immunological protection than did saponin. Experiments using PBMCs showed rLiHyE-stimulated lymphoproliferation in treated patients' and healthy subjects' cells, as well as high IFN-γ levels in the cell supernatant. In conclusion, rLiHyE could be considered for future studies as a vaccine candidate against VL.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos de Protozoários/administração & dosagem , Leishmania infantum/imunologia , Leishmaniose Visceral/prevenção & controle , Animais , Antígenos de Protozoários/imunologia , Feminino , Humanos , Imunogenicidade da Vacina , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Células Th1/imunologia , Vacinação
11.
Rev Soc Bras Med Trop ; 53: e20200091, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578713

RESUMO

INTRODUCTION: The drugs currently available for leishmaniasis treatment have major limitations. METHODS: In vitro and in vivo studies were performed to evaluate the effect of a quinoline derivative, Hydraqui (7-chloro-4-(3-hydroxy-benzilidenehydrazo)quinoline, against Leishmania amazonensis. In silico analyses of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were performed. RESULTS: Hydraqui showed significant in vitro anti-amastigote activity. Also, Hydraqui-treated mice exhibited high efficacy in lesion size (48.3%) and parasitic load (93.8%) reduction, did not cause hepatic and renal toxicity, and showed appropriate ADMET properties. CONCLUSIONS: Hydraqui presents a set of satisfactory criteria for its application as an antileishmanial agent.


Assuntos
Antiprotozoários/uso terapêutico , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Quinolinas/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Leishmaniose Cutânea/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Quinolinas/química
12.
BMC Infect Dis ; 20(1): 413, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539801

RESUMO

BACKGROUND: Successful control programs have impeded local malaria transmission in almost all Gulf Cooperation Council (GCC) countries: Qatar, Bahrain, Kuwait, Oman, the United Arab Emirates (UAE) and Saudi Arabia. Nevertheless, a prodigious influx of imported malaria via migrant workers sustains the threat of local transmission. Here we examine the origin of imported malaria in Qatar, assess genetic diversity and the prevalence of drug resistance genes in imported Plasmodium falciparum, and finally, address the potential for the reintroduction of local transmission. METHODS: This study examined imported malaria cases reported in Qatar, between 2013 and 2016. We focused on P. falciparum infections and estimated both total parasite and gametocyte density, using qPCR and qRT-PCR, respectively. We also examined ten neutral microsatellites and four genes associated with drug resistance, Pfmrp1, Pfcrt, Pfmdr1, and Pfkelch13, to assess the genetic diversity of imported P. falciparum strains, and the potential for propagating drug resistance genotypes respectively. RESULTS: The majority of imported malaria cases were P. vivax, while P. falciparum and mixed species infections (P. falciparum / P. vivax) were less frequent. The primary origin of P. vivax infection was the Indian subcontinent, while P. falciparum was mostly presented by African expatriates. Imported P. falciparum strains were highly diverse, carrying multiple genotypes, and infections also presented with early- and late-stage gametocytes. We observed a high prevalence of mutations implicated in drug resistance among these strains, including novel SNPs in Pfkelch13. CONCLUSIONS: The influx of genetically diverse P. falciparum, with multiple drug resistance markers and a high capacity for gametocyte production, represents a threat for the reestablishment of drug-resistant malaria into GCC countries. This scenario highlights the impact of mass international migration on the reintroduction of malaria to areas with absent or limited local transmission.


Assuntos
Doenças Transmissíveis Importadas/transmissão , Resistência a Medicamentos/genética , Malária/transmissão , Plasmodium falciparum/genética , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/parasitologia , Variação Genética , Genótipo , Humanos , Malária/epidemiologia , Malária/parasitologia , Carga Parasitária , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Prevalência , Catar/epidemiologia
13.
Parasitol Res ; 119(10): 3369-3376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32556502

RESUMO

Toxocara canis is a common parasite of dogs and can cause zoonotic toxocariasis in humans. As a part of control programs for this agent, optimized hygiene including chemical disinfection is considered essential in the prevention and control of zoonotic toxocariasis in humans. However, commonly used disinfectants at present mostly fail to inhibit the embryogenesis and viability of T. canis eggs. To this effect, the present study was designed to evaluate the effect of a chlorocresol-based disinfectant product Neopredisan®135-1 (NP) on embryonic development of T. canis eggs in vitro and to investigate the infectivity of exposed eggs by assessing larval establishment in a mouse model. Under in vitro conditions, NP at a final concentration of 0.25, 0.50, 1, 2, or 4% all exhibited significant killing effect on T. canis embryogenesis compared with the control eggs (P < 0.05), regardless of contact times (30, 60, 90, or 120 min). Such killing activity increased in a concentration- and time-dependent manner, with a maximum killing efficacy of 95.81% at 4% concentration and 120 min exposure time. Comparisons between low and high concentrations and between short and long contact times concluded that a protocol using the 1% concentration of NP with a 90-min contact could be the most suitable for practical application. Additionally, the lower larval recovery in mice inoculated with eggs treated by either 0.25 or 0.5% NP than that from their corresponding controls (P < 0.05) verified once again that NP had an adverse impact on the larval development of T. canis eggs even at a low concentration. To the best of our knowledge, this is the first study to report the effect of the chlorocresol-based disinfectant NP on the embryonation and larval development of T. canis eggs, and the results presented here would contribute to environmental clearance and control of toxocariasis by providing an alternative disinfectant resource. However, it is highlighted that the clearance of the novel and existing sources of infection including larvated eggs in places treated with NP is not guaranteed and therefore continuous monitoring and additional disinfection are still required.


Assuntos
Antinematódeos/farmacologia , Cresóis/farmacologia , Desinfetantes/farmacologia , Toxocara canis/efeitos dos fármacos , Toxocaríase/prevenção & controle , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Camundongos , Óvulo/efeitos dos fármacos , Óvulo/crescimento & desenvolvimento , Carga Parasitária , Toxocara canis/crescimento & desenvolvimento , Toxocaríase/parasitologia
14.
Parasitol Res ; 119(8): 2659-2666, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32529297

RESUMO

Blood samples from 72 Ameiva ameiva lizards from Central Amazonian upland forests were collected, and thin smears of 40 (55.5%) animals were positive for gamonts of Hepatozoon with a mean level of intensity of infection of 14 parasites/2000 blood erythrocytes (0.73%). The gametocytes were found attached with host cells' nuclei, and their dimensions were 14.28 ± 1.05 µm in length and 4.50 ± 0.80 µm in width. Phylogenetic analyses of the 18S rRNA gene showed that the new sequences obtained from A. ameiva constitute a monophyletic sister clade to the Hepatozoon spp. from Brazilian snakes. Based on morphological features and new molecular data, we redescribe this hemogregarine as Hepatozoon ameivae. This study also provides the first molecular characterization of a Hepatozoon species from a Brazilian lizard.


Assuntos
Coccidiose/veterinária , Eucoccidiida/classificação , Lagartos/parasitologia , Animais , Brasil , Coccidiose/parasitologia , Eritrócitos/parasitologia , Eucoccidiida/citologia , Eucoccidiida/genética , Eucoccidiida/crescimento & desenvolvimento , Estágios do Ciclo de Vida , Carga Parasitária , Filogenia , RNA Ribossômico 18S/genética
15.
PLoS Negl Trop Dis ; 14(6): e0008311, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32497037

RESUMO

BACKGROUND: Trypanosoma cruzi has a high genetic and biological diversity and has been subdivided into seven genetic lineages, named TcI-TcVI and TcBat. DTUs TcI-TcII-TcV and TcVI are agents of ChD in different regions of Latin America. Due to population movements, the disease is an emergent global public health problem. Thus, the aim of this study was to quantify the parasitic load and identify the presence of T. cruzi DTUs in 101 Latin American immigrants with chronic ChD, residing in Barcelona, Spain. METHODOLOGY / PRINCIPAL FINDINGS: 5ml of peripheral blood were collected in guanidine/EDTA from each patient for DNA extraction, quantification of the parasitic load and genotyping. A great variation of the parasitic load of the patients was verified: from 0.001 to 22.2 T. cruzi DNA (fg) / Blood DNA (ng). In patients from Bolivia the parasitic load was 3.76±4.43 T. cruzi DNA (fg) / Blood DNA (ng) (mean ± SD), in patients of other countries was 0.95±1.38 T. cruzi DNA (fg) / Blood DNA (ng). No statistically significant difference was observed in the parasitic load between patients with the indeterminate and cardiac forms of ChD (p = 0,57). Parasite genotyping was performed by multilocus conventional PCR. In patients from Bolivia there was a nearly equal prevalence of DTUs TcV (27/77), TcII/TcV/TcVI (26/77), and TcII/TcVI (22/77). TcVI was detected in only 2 samples (2/77). A higher prevalence of TcII/TcVI (19/24) was verified in patients of other countries, with low prevalence of TcII/TcV/TcVI (4/24) and TcV (1/24). CONCLUSIONS/SIGNIFICANCE: In this study, low/medium parasitic load was found in all patients evaluated. Our data corroborate previous conclusions indicating that patients from the Bolivia, living in Spain, are predominantly infected by TcV, and TcVI DTUs. On the other hand, in Non-Bolivians patients TcII/TcVI predominated. Surprisingly, in our cohort of 101 patients no infection by TcI DTU was observed.


Assuntos
Doença de Chagas/etnologia , Doença de Chagas/parasitologia , DNA de Protozoário/genética , Emigrantes e Imigrantes , Trypanosoma cruzi/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bolívia/etnologia , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Carga Parasitária , Análise de Sequência de DNA , Espanha/epidemiologia , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
16.
Parasite Immunol ; 42(9): e12733, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32418230

RESUMO

AIMS: Industrial growth has increased the exposure to endocrine disruptor compounds (EDCs) in all organisms. Bisphenol A (BPA), an EDC, has been demonstrated to be involved in the susceptibility to parasite infections. However, few studies have analysed this connection in more depth. The aim of this study was to determine whether early BPA exposure in female mice affects the systemic immune response and the susceptibility to Taenia crassiceps infection. METHODS AND RESULTS: BALB/c mice were exposed to BPA at post-natal day 3. At 6 weeks of age, they were inoculated with T crassiceps larvae and, 2 weeks later, were euthanized. The number of parasites was quantified. By flow cytometry, in the spleen, the peripheral and mesenteric lymph nodes, the different innate and adaptive immune cell modulation was analysed, and RT-PCR cytokine expression was also evaluated. BPA induced a reduction of 40% in parasite load. BPA treatment modulated some lineages of the innate immune response and caused slight changes in cells belonging to the adaptive immune response. Additionally, BPA enhanced the type 2 cytokine profile. CONCLUSION: Neonatal BPA treatment in female mice affects not only the percentage of different immune cells but also their ex vivo cytokine gene expression, decreasing T crassiceps cysticercosis susceptibility.


Assuntos
Anti-Helmínticos/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Cisticercose/prevenção & controle , Fenóis/uso terapêutico , Taenia/imunologia , Animais , Cisticercose/imunologia , Cisticercose/parasitologia , Citocinas/metabolismo , Feminino , Linfonodos , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Baço/imunologia , Teníase/imunologia , Teníase/prevenção & controle
17.
Am J Trop Med Hyg ; 103(1): 415-420, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32394882

RESUMO

Failures of primaquine for the treatment of relapsed Plasmodium vivax malaria is a serious challenge to malaria elimination in Ethiopia, where P. vivax accounts for up to 40% of malaria infections. We report here occurrence of a total of 15 episodes of primaquine treatment failure for radical cure in three historical P. vivax malaria patients from Gambella, Ethiopia, during 8-16 months of follow-up in 1985-1987. The total primaquine doses received were 17.5 mg/kg, 25.8 mg/kg, and 35.8 mg/kg, respectively. These total doses are much higher than in previous reports of patients with treatment failure in Ethiopia and East Africa. The possibility of new infection was excluded for these cases as the treatment and follow-up were carried out in Addis Ababa, a malaria-free city. Recrudescences were unlikely, considering the short duration pattern of the recurrences. The cytochrome P450 2D6 (CYP2D6) status for these patients is unknown, but polymorphisms have been described in Ethiopia and may have contributed to primaquine treatment failures. It is suggested that further studies be carried out in Ethiopia to determine the prevalence and distribution of primaquine treatment failures in different ethnic groups, considering the impact of CYP2D6 polymorphisms and the potential value of increasing the primaquine dose to avoid relapse.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Malária Vivax/tratamento farmacológico , Primaquina/uso terapêutico , Adulto , Quimioprevenção , Etiópia , Humanos , Malária Vivax/prevenção & controle , Masculino , Pessoa de Meia-Idade , Carga Parasitária , Plasmodium vivax , Retratamento , Falha de Tratamento
19.
Parasitol Res ; 119(7): 2287-2298, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32468190

RESUMO

Toxoplasma gondii is an important zoonotic protozoan of the phylum Apicomplexa that can infect nearly all warm-blooded animals. The parasite can exist as the interconvertible tachyzoite or bradyzoite forms, leading to acute or latent infection, respectively. No drug has been reported to penetrate the cyst wall and reduce bradyzoite survival and proliferation till now. The transcriptional level of metacaspases 2 (TgMCA2) in T. gondii is significantly upregulated during the formation of bradyzoites in the Pru strain, indicating that it may play an important role in the formation of bradyzoites. To further explore the function of TgMCA2, we constructed a TgMCA2 gene-knockout variant of the Pru strain (Δmca2). Comparative analysis revealed that the proliferative capacity of Pru Δmca2 increased, while the invasion and egressing properties were not affected by the knockout. Further data shows that the tachyzoites of Δmca2 failed to induce differentiation and form bradyzoites in vitro, and the transcriptional levels of some of the bradyzoite-specific genes (such as BAG1, LDH2, and SAG4A) in Δmca2 were significantly lower compared with that in the Pru strain at the bradyzoite stage. In vivo, no cysts were detected in Δmca2-infected mice. Further determination of parasite burden in Δmca2- and Pru-infected mice brain tissue at the genetic level showed that the gene load was significantly lower than that in Pru. In summary, we confirmed that TgMCA2 contributes to the formation of bradyzoites, and could provide an important foundation for the development of attenuated vaccines for the prevention of T. gondii infection.


Assuntos
Estágios do Ciclo de Vida , Proteínas de Protozoários/metabolismo , Toxoplasma/enzimologia , Toxoplasma/crescimento & desenvolvimento , Animais , Encéfalo/parasitologia , Regulação da Expressão Gênica no Desenvolvimento , Estágios do Ciclo de Vida/genética , Camundongos , Encistamento de Parasitas/genética , Carga Parasitária , Proteínas de Protozoários/genética , Toxoplasma/genética , Toxoplasmose Animal/parasitologia
20.
PLoS Negl Trop Dis ; 14(4): e0008224, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32302296

RESUMO

Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multi-dimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5'-nitroimidazole-sensitive and -resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5'-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.


Assuntos
Antiparasitários/farmacologia , Química Click/métodos , Descoberta de Drogas/métodos , Giardia lamblia/efeitos dos fármacos , Indazóis/farmacologia , Proteínas de Protozoários/metabolismo , Animais , Antiparasitários/síntese química , Antiparasitários/uso terapêutico , Modelos Animais de Doenças , Feminino , Giardíase/tratamento farmacológico , Indazóis/síntese química , Indazóis/uso terapêutico , Intestino Delgado/parasitologia , Masculino , Camundongos Endogâmicos C57BL , Carga Parasitária , Ligação Proteica , Proteômica/métodos
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