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1.
PLoS Negl Trop Dis ; 14(7): e0008534, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735561

RESUMO

Mast cells are innate effector cells that due to their localization in the tissue form the first line of defense against parasites. We have previously shown that specifically mucosal mast cells were essential for the termination of the intestinal Strongyloides ratti infection. Here, we analyze the impact of mast cells on the immune response and defense against the tissue-dwelling filarial nematode Litomosoides sigmodontis using mast cell-deficient Cpa3cre mice. Despite an increase and an activation of mast cells at the site of infection in wildtype BALB/c mice the outcome of L. sigmodontis infection was not changed in mast cell-deficient BALB/c Cpa3cre mice. In Cpa3cre mice neither vascular permeability induced by blood-sucking mites nor the migration of L3 was altered compared to Cpa3 wildtype littermates. Worm burden in the thoracic cavity was alike in the presence and absence of mast cells during the entire course of infection. Although microfilaremiae in the peripheral blood increased in mast cell-deficient mice at some time points, the infection was cleared with comparable kinetics in the presence and absence of mast cells. Moreover, mast cell deficiency had no impact on the cytokine and antibody response to L. sigmodontis. In summary, our findings suggest that mast cells are not mandatory for the initiation of an appropriate immune response and host defense during L. sigmodontis infection in mice.


Assuntos
Filariose/imunologia , Filarioidea/imunologia , Mastócitos/fisiologia , Animais , Permeabilidade Capilar , Carboxipeptidases A/genética , Carboxipeptidases A/metabolismo , Filariose/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Infestações por Ácaros , Mutação
2.
PLoS Pathog ; 16(7): e1008623, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639986

RESUMO

Antibiotic treatment has emerged as a promising strategy to sterilize and kill filarial nematodes due to their dependence on their endosymbiotic bacteria, Wolbachia. Several studies have shown that novel and FDA-approved antibiotics are efficacious at depleting the filarial nematodes of their endosymbiont, thus reducing female fecundity. However, it remains unclear if antibiotics can permanently deplete Wolbachia and cause sterility for the lifespan of the adult worms. Concerns about resistance arising from mass drug administration necessitate a careful exploration of potential Wolbachia recrudescence. In the present study, we investigated the long-term effects of the FDA-approved antibiotic, rifampicin, in the Brugia pahangi jird model of infection. Initially, rifampicin treatment depleted Wolbachia in adult worms and simultaneously impaired female worm fecundity. However, during an 8-month washout period, Wolbachia titers rebounded and embryogenesis returned to normal. Genome sequence analyses of Wolbachia revealed that despite the population bottleneck and recovery, no genetic changes occurred that could account for the rebound. Clusters of densely packed Wolbachia within the worm's ovarian tissues were observed by confocal microscopy and remained in worms treated with rifampicin, suggesting that they may serve as privileged sites that allow Wolbachia to persist in worms while treated with antibiotic. To our knowledge, these clusters have not been previously described and may be the source of the Wolbachia rebound.


Assuntos
Brugia pahangi/microbiologia , Filariose/microbiologia , Filaricidas/farmacologia , Rifampina/farmacologia , Wolbachia/efeitos dos fármacos , Animais , Feminino , Gerbillinae
3.
PLoS Negl Trop Dis ; 14(4): e0008182, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32243453

RESUMO

BACKGROUND: Studies of the human filarial parasite have been hampered by the fact that they are obligate parasites with long life cycles. In other pathogenic infections, in vivo imaging systems (IVIS) have proven extremely useful in studying pathogenesis, tissue tropism and in vivo drug efficacy. IVIS requires the use of transgenic parasites expressing a florescent reporter. Developing a method to produce transgenic filarial parasites expressing a florescent reporter would permit IVIS to be applied to the study of tissue tropism and provide a non-invasive way to screen for in vivo drug efficacy against these parasites. METHODOLOGY/PRINCIPAL FINDINGS: We report the development of a dual luciferase reporter construct in a piggyBac backbone that may be used to stably transfect Brugia malayi, a causative agent of human filariasis. Parasites transfected with this construct were visible in IVIS images obtained from infected gerbils. The signal in these infected animals increased dramatically when the transgenic parasites matured to the adult stage and began to produce transgenic progeny microfilaria. We demonstrate that the IVIS system can be used to develop an effective method for cryopreservation of transgenic parasites, to non-invasively monitor the effect of treatment with anti-filarial drugs, and to rapidly identify transgenic F1 microfilariae. CONCLUSIONS: To our knowledge, this represents the first application of IVIS to the study of a human filarial parasite. This method should prove useful in studies of tissue tropism and as an efficient in vivo assay for candidate anti-filarial drugs.


Assuntos
Brugia Malayi/genética , Elementos de DNA Transponíveis , Transfecção/métodos , Imagem Corporal Total , Animais , Animais Geneticamente Modificados , Brugia Malayi/crescimento & desenvolvimento , Criopreservação , Filariose/parasitologia , Gerbillinae , Humanos , Luciferases/genética , Luciferases/metabolismo , Masculino , Microfilárias/genética , Microfilárias/crescimento & desenvolvimento , Plasmídeos/genética , Plasmídeos/metabolismo
4.
Am J Trop Med Hyg ; 103(1): 480-484, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342844

RESUMO

The female immigrant population is especially vulnerable to imported diseases. We describe the results of a prospective screening program for imported diseases performed in immigrant female patients. The protocol included tests for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, Trypanosoma cruzi, Strongyloides stercoralis and Schistosoma spp., intestinal parasites, malaria, and the detection of microfilaremia, according to the patient's origin. Six hundred eleven patients were studied. The most frequent imported diseases were intestinal parasitosis (39.4%), followed by syphilis (14.6%), HIV infection (9%), chronic HCV (5%), and HBV (3.3%). Most of the cases of HIV (78%) and HBV (85%) were diagnosed in patients aged between 16 and 45 years. Hepatitis C virus appeared mostly in patients in the 46- to 65-year range (P = 0.001; odds ratio [OD]: 3.667 [1.741-7.724]) or older than 65 years (P = 0.0001; OR: 26.350 [7.509-92.463]). Syphilis was diagnosed more frequently in patients older than 46 years (P = 0.0001; OR: 4.273 [2.649-6.893]). Multivariate analysis confirmed a greater presence of HCV infection (P = 0.049) and syphilis (P = 0.0001) in patients aged between 46 and 65 years. In 15.4% of patients, screening did not find any pathology. These data show a high prevalence of imported diseases in the female immigrant population, which may have serious consequences in terms of morbimortality and vertical transmission. Our results encourage the establishment of policies of active screening both in women of childbearing age and within the specific pregnancy screening programs.


Assuntos
Doenças Transmissíveis Importadas/diagnóstico , Emigrantes e Imigrantes/estatística & dados numéricos , Mulheres , Adolescente , Adulto , África/etnologia , Idoso , América Central/etnologia , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doenças Transmissíveis Importadas/epidemiologia , Feminino , Filariose/diagnóstico , Filariose/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Humanos , Transmissão Vertical de Doença Infecciosa , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/epidemiologia , Malária/diagnóstico , Malária/epidemiologia , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Esquistossomose/diagnóstico , Esquistossomose/epidemiologia , América do Sul/etnologia , Espanha/epidemiologia , Estrongiloidíase/diagnóstico , Estrongiloidíase/epidemiologia , Sífilis/diagnóstico , Sífilis/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adulto Jovem
5.
Parasitol Res ; 119(4): 1301-1315, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32179986

RESUMO

Malaria and lymphatic filariasis (LF) are two leading and common mosquito-borne parasitic diseases worldwide. These two diseases are co-endemic in many tropical and sub-tropical regions and are known to share vectors. The interactions between malaria and filarial parasites are poorly understood. Thus, this study aimed at establishing the interactions that occur between Brugia pahangi and Plasmodium berghei ANKA (PbA) co-infection in gerbils. Briefly, the gerbils were matched according to age, sex, and weight and grouped into filarial-only infection, PbA-only infection, co-infection, and control group. The parasitemia, survival and clinical assessment of the gerbils were monitored for a period of 30 days post Plasmodium infection. The immune responses of gerbils to both mono and co-infection were monitored. Findings show that co-infected gerbils have higher survival rate than PbA-infected gerbils. Food and water consumption were significantly reduced in both PbA-infected and co-infected gerbils, although loss of body weight, hypothermia, and anemia were less severe in co-infected gerbils. Plasmodium-infected gerbils also suffered hypoglycemia, which was not observed in co-infected gerbils. Furthermore, gerbil cytokine responses to co-infection were significantly higher than PbA-only-infected gerbils, which is being suggested as a factor for their increased longevity. Co-infected gerbils had significantly elicited interleukin-4, interferon-gamma, and tumor necrotic factor at early stage of infection than PbA-infected gerbils. Findings from this study suggest that B. pahangi infection protect against severe anemia and hypoglycemia, which are manifestations of PbA infection.


Assuntos
Brugia pahangi/imunologia , Filariose/veterinária , Gerbillinae/parasitologia , Malária/veterinária , Plasmodium berghei/imunologia , Animais , Coinfecção/imunologia , Coinfecção/parasitologia , Citocinas/sangue , Feminino , Filariose/parasitologia , Interações Hospedeiro-Parasita/imunologia , Hipoglicemia/parasitologia , Malária/parasitologia , Masculino , Mosquitos Vetores/parasitologia , Parasitemia/parasitologia , Parasitemia/veterinária , Taxa de Sobrevida
6.
Parasite Immunol ; 42(7): e12708, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145033

RESUMO

Litomosoides sigmodontis is the only filarial nematode where the full life cycle, from larval delivery to the skin through to circulating microfilaria, can be completed in immunocompetent laboratory mice. It is thus an invaluable tool for the study of filariasis. It has been used for the study of novel anti-helminthic therapeutics, the development of vaccines against filariasis, the development of immunomodulatory drugs for the treatment of inflammatory disease and the study of basic immune responses to filarial nematodes. This review will focus on the latter and aims to summarize how the L sigmodontis model has advanced our basic understanding of immune responses to helminths, led to major discoveries in macrophage biology and provided new insights into the immunological functions of the pleural cavity. Finally, and most importantly L sigmodontis represents a suitable platform to study how host genotype affects immune responses, with the potential for further discovery in myeloid cell biology and beyond.


Assuntos
Filariose/imunologia , Filarioidea/imunologia , Interações Hospedeiro-Parasita/imunologia , Animais , Anti-Helmínticos/farmacologia , Modelos Animais de Doenças , Feminino , Filariose/tratamento farmacológico , Filariose/prevenção & controle , Genótipo , Interações Hospedeiro-Parasita/genética , Estágios do Ciclo de Vida , Camundongos , Camundongos Endogâmicos BALB C , Microfilárias/imunologia , Células Mieloides/imunologia
7.
PLoS Negl Trop Dis ; 14(2): e0008119, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32107497

RESUMO

Neutrophils are essentially involved in protective immune responses against invading infective larvae of filarial nematodes. The present study investigated the impact of S100A8/S100A9 on protective immune responses against the rodent filarial nematode Litomosoides sigmodontis. S100A9 forms with S100A8 the heterodimer calprotectin, which is expressed by circulating neutrophils and monocytes and mitigates or amplifies tissue damage as well as inflammation depending on the immune environment. Mice deficient for S100A8/A9 had a significantly reduced worm burden in comparison to wildtype (WT) animals 12 days after infection (dpi) with infective L3 larvae, either by the vector or subcutaneous inoculation, the latter suggesting that circumventing natural immune responses within the epidermis and dermis do not alter the phenotype. Nevertheless, upon intradermal injection of L3 larvae, increased total numbers of neutrophils, eosinophils and macrophages were observed within the skin of S100A8/A9-/- mice. Furthermore, upon infection the bronchoalveolar and thoracic cavity lavage of S100A8/A9-/- mice showed increased concentrations of CXCL-1, CXCL-2, CXCL-5, as well as elastase in comparison to the WT controls. Neutrophils from S100A8/A9-/- mice exhibited an increased in vitro activation and reduced L3 larval motility more effectively in vitro compared to WT neutrophils. The depletion of neutrophils from S100A8/A9-/- mice prior to L. sigmodontis infection until 5dpi abrogated the protective effect and led to an increased worm burden, indicating that neutrophils mediate enhanced protective immune responses against invading L3 larvae in S100A8/A9-/- mice. Interestingly, complete circumvention of protective immune responses in the skin and the lymphatics by intravenous injection of L3 larvae reversed the phenotype and resulted in an increased worm burden in S100A8/A9-/- mice. In summary, our results reveal that lack of S100A8/S100A9 triggers L3-induced inflammatory responses, increasing chemokine levels, granulocyte recruitment as well as neutrophil activation and therefore impairs larval migration and susceptibility for filarial infection.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Filariose/imunologia , Filarioidea/imunologia , Animais , Regulação da Expressão Gênica , Larva/imunologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Neutrófilos/fisiologia
8.
PLoS Negl Trop Dis ; 14(1): e0007957, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31986143

RESUMO

The elimination of filarial diseases such as onchocerciasis and lymphatic filariasis is hampered by the lack of a macrofilaricidal-adult worm killing-drug. In the present study, we tested the in vivo efficacy of AN11251, a boron-pleuromutilin that targets endosymbiotic Wolbachia bacteria from filarial nematodes and compared its efficacy to doxycycline and rifampicin. Doxycycline and rifampicin were previously shown to deplete Wolbachia endosymbionts leading to a permanent sterilization of the female adult filariae and adult worm death in human clinical studies. Twice-daily oral treatment of Litomosoides sigmodontis-infected mice with 200 mg/kg AN11251 for 10 days achieved a Wolbachia depletion > 99.9% in the adult worms, exceeding the Wolbachia reduction by 10-day treatments with bioequivalent human doses of doxycycline and a similar reduction as high-dose rifampicin (35 mg/kg). Wolbachia reductions of > 99% were also accomplished by 14 days of oral AN11251 at a lower twice-daily dose (50 mg/kg) or once-per-day 200 mg/kg AN11251 treatments. The combinations tested of AN11251 with doxycycline had no clear beneficial impact on Wolbachia depletion, achieving a > 97% Wolbachia reduction with 7 days of treatment. These results indicate that AN11251 is superior to doxycycline and comparable to high-dose rifampicin in the L. sigmodontis mouse model, allowing treatment regimens as short as 10-14 days. Therefore, AN11251 represents a promising pre-clinical candidate that was identified in the L. sigmodontis model, and could be further evaluated and developed as potential clinical candidate for human lymphatic filariasis and onchocerciasis.


Assuntos
Antibacterianos/farmacologia , Diterpenos/farmacologia , Filariose/tratamento farmacológico , Filarioidea/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Wolbachia/efeitos dos fármacos , Animais , Boro , Doxiciclina/farmacologia , Feminino , Filariose/microbiologia , Filarioidea/microbiologia , Camundongos Endogâmicos BALB C , Rifampina/farmacologia , Simbiose
9.
Am J Trop Med Hyg ; 102(3): 578-581, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31933469

RESUMO

This study investigated the applications of recombinant monoclonal antibodies (rmAbs) produced against two recombinant filarial proteins of diagnostic value. Ab5B and Ab3A were produced against recombinant BmSXP, and Ab4 and Ab4-fragment crystallizable (Fc) against recombinant BmR1. Ab5B and Ab4-Fc were found to be useful as quality control (QC) reagents for two commercial rapid test kits, such as Brugia RapidTM and BLF Rapid® (Reszon Diagnostics International Sdn. Bhd., 47600 Subang Jaya, Selangor, Malaysia), respectively. The two rmAbs reacted positively with the corresponding recombinant proteins lined on the nitrocellulose strips of the cassette tests, thus may replace or reduce the need for patient serum samples as positive controls for QC of the commercial kits. They were also successfully conjugated to gold nanoparticles and reacted positively with the test lines containing the corresponding recombinant proteins when directly applied to the cassette tests. The gold-conjugated reagents can be used to confirm the antigenicity of test lines after the storage of the rapid tests for a prolonged period or under unfavorable conditions. Furthermore, Ab5B and Ab3A were shown to be able to capture the target recombinant proteins through immunoaffinity purification, enabling their use for applications that need very highly purified proteins. In conclusion, this study demonstrated several potential uses of rmAb proteins produced against recombinant filarial proteins.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Anticorpos Monoclonais , Antígenos de Helmintos/sangue , Filariose/diagnóstico , Técnicas de Visualização da Superfície Celular , Regulação da Expressão Gênica , Coloide de Ouro , Células HEK293 , Humanos , Imunoensaio
10.
Parasit Vectors ; 12(1): 580, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829219

RESUMO

BACKGROUND: Parafilaria bovicola (Nematoda: Filariidae) causes cutaneous bleedings in bovine species. Flies serve as intermediate hosts. In recent years, reports on bovine parafilariosis have become more frequent, corroborating the necessity of reliable diagnostic interventions especially since no molecular or serological test has been available. We aimed to establish a polymerase chain reaction assay to detect DNA of P. bovicola in flies, skin biopsies and serohemorraghic exudates of bleeding spots. METHODS: PCRs targeting the cytochrome c oxidase subunit 1 (cox1) gene and the internal transcribed spacer region (ITS) of the ribosomal RNA gene cluster were evaluated for their diagnostic sensitivity as well as performance and specificity on biopsy and serohemorrhagic exudate samples from P. bovicola-infected cattle. RESULTS: Using serohemorrhagic exudates (n = 6), biopsies (n = 2) and flies (n = 1), the PCR targeting the cox1 gene resulted in a gel band of almost 700 bp. Cloning, sequencing, and removal of primer sequences yielded a 649-bp fragment of the P. bovicola cox1 gene. The PCR targeting the ITS region showed a band of about 1100 bp. Cloning, sequencing, and removal of primer sequences resulted in a 1083 bp stretch of the P. bovicola ITS region. Testing samples from presumably affected animals, the cox1-PCR resulted in bands with the expected size and they were all confirmed as P. bovicola by sequencing. In contrast, the ITS-PCR proved to be less sensitive and less specific and additionally amplified the ITS region of Musca domestica or buttercup DNA. When analysing for sensitivity, the cox1-PCR yielded visible bands up to 2 ng of genomic DNA, whereas the ITS-PCR produced bands up to 3 ng. In a plasmid dilution series, the minimum number of target DNA copies was 102 for the cox1-PCR and 101 in the ITS-PCR. CONCLUSIONS: The evaluated cox1-PCR enables reliable detection of P. bovicola DNA in skin biopsies and serohemorrhagic exudates. This PCR and, to a limited extent, the ITS-PCR, may help evaluate different therapeutic approaches. Furthermore, the cox1-PCR may be useful for epidemiological studies on the geographical distribution of P. bovicola. Further understanding of the epidemiology of this parasite will help develop and implement effective control strategies.


Assuntos
Doenças dos Bovinos/diagnóstico , DNA Espaçador Ribossômico/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Filariose/veterinária , Filarioidea/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Animais , Biópsia , Bovinos , Doenças dos Bovinos/parasitologia , Exsudatos e Transudatos/parasitologia , Filariose/diagnóstico , Filariose/parasitologia , Filarioidea/enzimologia , Filarioidea/genética , Sensibilidade e Especificidade , Pele/parasitologia
11.
PLoS Negl Trop Dis ; 13(12): e0007908, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31815932

RESUMO

T cell-intrinsic regulation, such as anergy, adaptive tolerance and exhaustion, is central to immune regulation. In contrast to Type 1 and Type 17 settings, knowledge of the intrinsic fate and function of Th2 cells in chronic Type 2 immune responses is lacking. We previously showed that Th2 cells develop a PD-1/PD-L2-dependent intrinsically hypo-responsive phenotype during infection with the filarial nematode Litomosoides sigmodontis, denoted by impaired functionality and parasite killing. This study aimed to elucidate the transcriptional changes underlying Th2 cell-intrinsic hypo-responsiveness, and whether it represents a unique and stable state of Th2 cell differentiation. We demonstrated that intrinsically hypo-responsive Th2 cells isolated from L. sigmodontis infected mice stably retained their dysfunctional Th2 phenotype upon transfer to naïve recipients, and had a divergent transcriptional profile to classical Th2 cells isolated prior to hypo-responsiveness and from mice exposed to acute Type 2 stimuli. Hypo-responsive Th2 cells displayed a distinct transcriptional profile to exhausted CD4+ T cells, but upregulated Blimp-1 and the anergy/regulatory-associated transcription factors Egr2 and c-Maf, and shared characteristics with tolerised T cells. Hypo-responsive Th2 cells increased mRNA expression of the soluble regulatory factors Fgl2, Cd38, Spp1, Areg, Metrnl, Lgals3, and Csf1, and a subset developed a T-bet+IFN-γ+ Th2/Th1 hybrid phenotype, indicating that they were not functionally inert. Contrasting with their lost ability to produce Th2 cytokines, hypo-responsive Th2 cells gained IL-21 production and IL-21R blockade enhanced resistance to L. sigmodontis. IL-21R blockade also increased the proportion of CD19+PNA+ germinal centre B cells and serum levels of parasite specific IgG1. This indicates a novel regulatory role for IL-21 during filarial infection, both in controlling protection and B cell responses. Thus, Th2 cell-intrinsic hypo-responsiveness is a distinct and stable state of Th2 cell differentiation associated with a switch from a classically active IL-4+IL-5+ Th2 phenotype, to a non-classical dysfunctional and potentially regulatory IL-21+Egr2+c-Maf+Blimp-1+IL-4loIL-5loT-bet+IFN-γ+ Th2 phenotype. This divergence towards alternate Th2 phenotypes during chronicity has broad implications for the outcomes and treatment of chronic Type 2-related infections and diseases.


Assuntos
Antígenos de Helmintos/imunologia , Filariose/patologia , Filarioidea/imunologia , Células Th2/imunologia , Animais , Modelos Animais de Doenças , Feminino , Filariose/imunologia , Perfilação da Expressão Gênica , Camundongos Endogâmicos BALB C , Fenótipo , Células Th2/patologia
12.
Arq. bras. med. vet. zootec. (Online) ; 71(6): 1944-1949, Nov.-Dec. 2019. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1055130

RESUMO

Stephanofilariasis is an ulcerative dermatitis caused by nematodes that affect cattle in several countries in the world. However, it has not been described in beef cattle in Brazil. The objective of this study is to describe three cases of stephanofilariasis, which occurred in beef cows in the municipality of Ipê, RS, Brazil. The disease was characterized by pruritic, ulcerated and crusty seasonal lesions present in the cranial region of the udder. The diagnosis was confirmed by analyses of secretions stained smears and by direct optical microscopic examination of the sediment and the treatment was effectively carried out with topical trichlorphon. This report indicates that stephanofilariasis should be included as a differential diagnosis for dermatopathies in beef cattle in Brazil.(AU)


A estefanofilariose é uma dermatite ulcerativa causada por nematódeos que acometem bovinos em vários países do mundo, no entanto não tem sido descrita em bovinos de corte no Brasil. O objetivo do trabalho é a descrição de três casos de estefanofilariose em vacas de corte ocorridos no município de Ipê, RS. A enfermidade foi caracterizada por lesões sazonais pruriginosas, ulceradas e crostosas, presentes na região cranial do úbere. O diagnóstico foi confirmado pela análise dos esfregaços corados das secreções e por exame direto do sedimento em microscopia óptica, e o tratamento foi realizado de maneira eficaz com triclorfon tópico. Este relato demonstra que a estefanofilariose deve ser incluída como diagnóstico diferencial nas dermatopatias em bovinos de corte no Brasil.(AU)


Assuntos
Animais , Feminino , Bovinos , Dermatite/veterinária , Filariose/veterinária , Transtornos da Lactação/veterinária , Infecções por Nematoides/veterinária
13.
Washington, D.C.; OPS; 2019-12-11.
em Francês | PAHO-IRIS | ID: phr-51761

RESUMO

[Antécédents]: Le présent document rassemble une série de recommandations émises par l’Organisation mondiale de la Santé (OMS) et l’Organisation panaméricaine de la Santé (OPS) pour aider les professionnels chargés des programmes de lutte antivectorielle en Amérique latine et dans les Caraïbes aux niveaux national, infranational et local à mettre à jour et prendre des decisions à base factuelle qui touchent les mesures de lutte antivectorielle les mieux adaptées à chaque situation particulière. La GIV peut être utilisée lorsque la cible est la surveillance et la lutte ou l’élimination (en function de chaque situation) des MTV et peut contribuer à réduire le développement de la résistance aux insecticides au moyen de l’utilisation rationnelle de ces produits. Le présent document contient les instructions nécessaires pour mener à bien le mandat établi par l’OPS en 2008 (résolution CD48.R8, document CD48/13), en particulier, il complémente une série de guides de l’OMS publiés en 2012 : le manuel pour la GIV et les guides de suivi et d’évaluation des indicateurs de GIV, l’élaboration de politiques pour la GIV et les programmes de formation à la GIV. L’élaboration du document repose sur une méthodologie orientée de sorte à obtenir les meilleures données factuelles disponibles sur la GIV en tenant compte de la situation réelle des pays et des principaux scénarios de transmission des MTV. L’auteur espère que ce document opérationnel sera reproductible et d’application facile, et que les messages qui y figurent seront clairs, de sorte que la mise en oeuvre de la GIV soit aussi efficace que possible dans les régions respectives. Les annexes font état de l’expérience acquise par différents pays de la Région où les concepts de la GIV sont actuellement appliqués.


Assuntos
Controle de Vetores , Dengue , Zika virus , Vírus Chikungunya , Doença de Chagas , Leishmaniose , Filariose
14.
PLoS Negl Trop Dis ; 13(11): e0007811, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31770367

RESUMO

BACKGROUND: The release of small non-coding RNAs (sRNAs) has been reported in parasitic nematodes, trematodes and cestodes of medical and veterinary importance. However, little is known regarding the diversity and composition of sRNAs released by different lifecycle stages and the portion of sRNAs that persist in host tissues during filarial infection. This information is relevant to understanding potential roles of sRNAs in parasite-to-host communication, as well as to inform on the location within the host and time point at which they can be detected. METHODOLOGY AND PRINCIPAL FINDINGS: We have used small RNA (sRNA) sequencing analysis to identify sRNAs in replicate samples of the excretory-secretory (ES) products of developmental stages of the filarial nematode Litomosoides sigmodontis in vitro and compare this to the parasite-derived sRNA detected in host tissues. We show that all L. sigmodontis developmental stages release RNAs in vitro, including ribosomal RNA fragments, 5'-derived tRNA fragments (5'-tRFs) and, to a lesser extent, microRNAs (miRNAs). The gravid adult females (gAF) produce the largest diversity and abundance of miRNAs in the ES compared to the adult males or microfilariae. Analysis of sRNAs detected in serum and macrophages from infected animals reveals that parasite miRNAs are preferentially detected in vivo, compared to their low levels in the ES products, and identifies miR-92-3p and miR-71-5p as L. sigmodontis miRNAs that are stably detected in host cells in vivo. CONCLUSIONS: Our results suggest that gravid adult female worms secrete the largest diversity of extracellular sRNAs compared to adult males or microfilariae. We further show differences in the parasite sRNA biotype distribution detected in vitro versus in vivo. We identify macrophages as one reservoir for parasite sRNA during infection, and confirm the presence of parasite miRNAs and tRNAs in host serum during patent infection.


Assuntos
Filariose/genética , Filarioidea/genética , Filarioidea/fisiologia , Interações Hospedeiro-Parasita/fisiologia , Pequeno RNA não Traduzido/sangue , Animais , Líquidos Corporais , Feminino , Filariose/parasitologia , Estágios do Ciclo de Vida , Macrófagos , Masculino , Camundongos , MicroRNAs/genética , Microfilárias , RNA Ribossômico , RNA de Transferência , Análise de Sequência
15.
Afr J Prim Health Care Fam Med ; 11(1): e1-e4, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31714130

RESUMO

Although Sierra Leone lies within the worldwide filarial belt, chyluria (the passage of milky coloured urine) is a rare presenting symptom in clinical practice. This report describes a confirmed case of parasitic filariasis presenting in a 72-year-old woman. After treatment with a combination of ivermectin and albendazole, her symptoms resolved within 48 h and she was symptom free at 6 months.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Quilo/efeitos dos fármacos , Filariose/tratamento farmacológico , Ivermectina/uso terapêutico , Nefropatias/tratamento farmacológico , Idoso , Feminino , Humanos , Resultado do Tratamento
16.
BMJ Case Rep ; 12(10)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645405

RESUMO

Filariasis, a neglected tropical disease (NTD), is mainly caused by nematodes-Wuchereria bancrofti, Brugia malayi and B. timori Apart from profoundly disabling and disfiguring major clinical manifestations-lymphoedema, elephantiasis and hydrocoele-asymptomatic microfilaremia is common in endemic areas. Despite this, it is very rare to detect microfilariae in body fluids or aspirates. As per the literature search, this is the third case documenting incidental detection of microfilariae with metastatic deposits in the liver aspirate. Here, a 35-year-old man underwent image-guided fine-needle aspiration cytology of liver nodule. Liver aspirate cytology revealed poorly differentiated mucin-secreting metastatic carcinoma and coincidental presence of microfilariae of W. bancrofti Recently, microfilaria has frequently been found to be associated with the debilitated, immunocompromised condition and various neoplasm/cancer/malignancy. Hence, meticulous investigation should be undertaken to search for hidden pathology, whenever microfilariae are detected; and to deeply scrutinise aspirates for such parasites always, especially in endemic regions.


Assuntos
Filariose/complicações , Neoplasias Hepáticas/complicações , Wuchereria bancrofti/isolamento & purificação , Adulto , Animais , Biópsia por Agulha Fina , Evolução Fatal , Filariose/diagnóstico , Filariose/patologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Microfilárias/isolamento & purificação
17.
PLoS Pathog ; 15(9): e1008085, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31568486

RESUMO

Human parasitic nematodes are the causative agents of lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness), diseases that are endemic to more than 80 countries and that consistently rank in the top ten for the highest number of years lived with disability. These filarial nematodes have evolved an obligate mutualistic association with an intracellular bacterium, Wolbachia, a symbiont that is essential for the successful development, reproduction, and survival of adult filarial worms. Elimination of the bacteria causes adult worms to die, making Wolbachia a primary target for developing new interventional tools to combat filariases. To further explore Wolbachia as a promising indirect macrofilaricidal drug target, the essential cellular processes that define the symbiotic Wolbachia-host interactions need to be identified. Genomic analyses revealed that while filarial nematodes encode all the enzymes necessary for glycolysis, Wolbachia does not encode the genes for three glycolytic enzymes: hexokinase, 6-phosphofructokinase, and pyruvate kinase. These enzymes are necessary for converting glucose into pyruvate. Wolbachia, however, has the full complement of genes required for gluconeogenesis starting with pyruvate, and for energy metabolism via the tricarboxylic acid cycle. Therefore, we hypothesized that Wolbachia might depend on host glycolysis to maintain a mutualistic association with their parasitic host. We did conditional experiments in vitro that confirmed that glycolysis and its end-product, pyruvate, sustain this symbiotic relationship. Analysis of alternative sources of pyruvate within the worm indicated that the filarial lactate dehydrogenase could also regulate the local intracellular concentration of pyruvate in proximity to Wolbachia and thus help control bacterial growth via molecular interactions with the bacteria. Lastly, we have shown that the parasite's pyruvate kinase, the enzyme that performs the last step in glycolysis, could be a potential novel anti-filarial drug target. Establishing that glycolysis is an essential component of symbiosis in filarial worms could have a broader impact on research focused on other intracellular bacteria-host interactions where the role of glycolysis in supporting intracellular survival of bacteria has been reported.


Assuntos
Brugia/metabolismo , Brugia/microbiologia , Ácido Pirúvico/metabolismo , Wolbachia/metabolismo , Animais , Brugia/genética , Brugia Malayi/genética , Brugia Malayi/metabolismo , Brugia Malayi/microbiologia , Brugia pahangi/genética , Brugia pahangi/metabolismo , Brugia pahangi/microbiologia , Feminino , Filariose/metabolismo , Filariose/microbiologia , Filariose/parasitologia , Genes de Helmintos , Glicólise , Interações entre Hospedeiro e Microrganismos , Interações Hospedeiro-Parasita , Humanos , Masculino , Simbiose , Wolbachia/genética
19.
PLoS Pathog ; 15(9): e1008041, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31553770

RESUMO

Filariae are parasitic nematodes that are transmitted to their definitive host as third-stage larvae by arthropod vectors like mosquitoes. Filariae cause diseases including: lymphatic filariasis with distressing and disturbing symptoms like elephantiasis; and river blindness. Filarial diseases affect millions of people in 73 countries throughout the topics and sub-tropics. The drugs available for mass drug administration, (ivermectin, albendazole and diethylcarbamazine), are ineffective against adult filariae (macrofilariae) at the registered dosing regimen; this generates a real and urgent need to identify effective macrofilaricides. Emodepside, a veterinary anthelmintic registered for treatment of nematode infections in cats and dogs, is reported to have macrofilaricidal effects. Here, we explore the mode of action of emodepside using adult Brugia malayi, one of the species that causes lymphatic filariasis. Whole-parasite motility measurement with Worminator and patch-clamp of single muscle cells show that emodepside potently inhibits motility by activating voltage-gated potassium channels and that the male is more sensitive than the female. RNAi knock down suggests that emodepside targets SLO-1 K channels. We expressed slo-1 isoforms, with alternatively spliced exons at the RCK1 (Regulator of Conductance of Potassium) domain, heterologously in Xenopus laevis oocytes. We discovered that the slo-1f isoform, found in muscles of males, is more sensitive to emodepside than the slo-1a isoform found in muscles of females; and selective RNAi of the slo-1a isoform in female worms increased emodepside potency. In Onchocerca volvulus, that causes river blindness, we found two isoforms in adult females with homology to Bma-SLO-1A and Bma-SLO-1F at the RCK1 domain. In silico modeling identified an emodepside binding pocket in the same RCK1 region of different species of filaria that is affected by these splice variations. Our observations show that emodepside has potent macrofilaricidal effects and alternative splicing in the RCK1 binding pocket affects potency. Therefore, the evaluation of potential sex-dependent effects of an anthelmintic compound is of importance to prevent any under-dosing of one or the other gender of nematodes once given to patients.


Assuntos
Brugia Malayi/efeitos dos fármacos , Brugia Malayi/fisiologia , Depsipeptídeos/farmacologia , Filaricidas/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sítios de Ligação/genética , Brugia Malayi/genética , Feminino , Filariose/tratamento farmacológico , Filariose/parasitologia , Técnicas de Silenciamento de Genes , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Alta/química , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Modelos Moleculares , Movimento/efeitos dos fármacos , Movimento/fisiologia , Músculos/efeitos dos fármacos , Músculos/fisiologia , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Homologia de Sequência de Aminoácidos , Fatores Sexuais
20.
Epidemiol Infect ; 147: e260, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31475670

RESUMO

Filariasis is one of the major public health concerns in India. Approximately 600 million people spread across 250 districts of India are at risk of filariasis. To predict this disease, a pilot scale study was carried out in 30 villages of Karimnagar district of Telangana from 2004 to 2007 to collect epidemiological and socio-economic data. The collected data are analysed by employing various machine learning techniques such as Naïve Bayes (NB), logistic model tree, probabilistic neural network, J48 (C4.5), classification and regression tree, JRip and gradient boosting machine. The performances of these algorithms are reported using sensitivity, specificity, accuracy and area under ROC curve (AUC). Among all employed classification methods, NB yielded the best AUC of 64% and was equally statistically significant with the rest of the classifiers. Similarly, the J48 algorithm generated 23 decision rules that help in developing an early warning system to implement better prevention and control efforts in the management of filariasis.


Assuntos
Métodos Epidemiológicos , Filariose/epidemiologia , Aprendizado de Máquina , Modelos Estatísticos , Fatores Socioeconômicos , Humanos , Índia/epidemiologia , Curva ROC
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