RESUMO
While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.
Assuntos
Região 3'-Flanqueadora/genética , Genótipo , Antígenos HLA-G/genética , Leishmaniose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
OBJECTIVES: The present study aims to describe the clinical, electrocardiographic, and echocardiographic cardiological findings in a group of patients with oral clefts. METHODS: This is a prospective cross-sectional study on 70 children (age range from 13 days to 19 years) with oral clefts who attended the multidisciplinary program of a university hospital from March 2013 to September 2014. The patients were evaluated by a pediatric cardiologist and underwent detailed anamnesis, physical examination, electrocardiogram, and echocardiogram. RESULTS: Sixty percent of the patients were male; 55.7% presented with cleft lip and palate, and 40.0% presented with health complaints. Comorbidities were found in 44.3%. Relevant pregnancy, neonatal, family and personal antecedents were present in 55.7%, 27.1%, 67.2%, and 24.3% of the patients, respectively. Regarding the antecedents, 15.2% of the patients presented with a cardiac murmur, 49.0% with a familial risk of developing plurimetabolic syndrome, and 6% with family antecedents of rheumatic fever. Electrocardiographic evaluation showed one case of atrioventricular block. Echocardiograms were abnormal in 35.7% of the exams, including 5 cases of mitral valve prolapse - one of which was diagnosed with rheumatic heart disease. CONCLUSION: The finding of a family risk of developing plurimetabolic syndrome and a diagnosis of rheumatic heart disease indicates that patients with oral clefts may be more prone to developing acquired heart disease. Thus, our findings highlight the importance of anamnesis and methodological triangulation (clinical-electrocardiographic-echocardiographic) in the investigation of patients with oral clefts and emphasize that cardiological follow-up to evaluate acquired and/or rhythm heart diseases is necessary. This strategy permits comorbidity prevention and individualized planned treatment.
Assuntos
Anormalidades Cardiovasculares/complicações , Fenda Labial/complicações , Fissura Palatina/complicações , Adolescente , Adulto , Anormalidades Cardiovasculares/diagnóstico por imagem , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia , Eletrocardiografia , Saúde da Família , Feminino , Comunicação Interventricular/complicações , Comunicação Interventricular/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome Metabólica/complicações , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: The present study aims to describe the clinical, electrocardiographic, and echocardiographic cardiological findings in a group of patients with oral clefts. METHODS: This is a prospective cross-sectional study on 70 children (age range from 13 days to 19 years) with oral clefts who attended the multidisciplinary program of a university hospital from March 2013 to September 2014. The patients were evaluated by a pediatric cardiologist and underwent detailed anamnesis, physical examination, electrocardiogram, and echocardiogram. RESULTS: Sixty percent of the patients were male; 55.7% presented with cleft lip and palate, and 40.0% presented with health complaints. Comorbidities were found in 44.3%. Relevant pregnancy, neonatal, family and personal antecedents were present in 55.7%, 27.1%, 67.2%, and 24.3% of the patients, respectively. Regarding the antecedents, 15.2% of the patients presented with a cardiac murmur, 49.0% with a familial risk of developing plurimetabolic syndrome, and 6% with family antecedents of rheumatic fever. Electrocardiographic evaluation showed one case of atrioventricular block. Echocardiograms were abnormal in 35.7% of the exams, including 5 cases of mitral valve prolapse — one of which was diagnosed with rheumatic heart disease. CONCLUSION: The finding of a family risk of developing plurimetabolic syndrome and a diagnosis of rheumatic heart disease indicates that patients with oral clefts may be more prone to developing acquired heart disease. Thus, our findings highlight the importance of anamnesis and methodological triangulation (clinical-electrocardiographic-echocardiographic) in the investigation of patients with oral clefts and emphasize that cardiological follow-up to evaluate acquired and/or rhythm heart diseases is necessary. This strategy permits comorbidity prevention and individualized planned treatment.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Fenda Labial/complicações , Fissura Palatina/complicações , Anormalidades Cardiovasculares/complicações , Índice de Gravidade de Doença , Ecocardiografia , Saúde da Família , Estudos Transversais , Estudos Prospectivos , Medição de Risco , Anormalidades Cardiovasculares/diagnóstico por imagem , Síndrome Metabólica/complicações , Eletrocardiografia , Comunicação Interventricular/complicações , Comunicação Interventricular/diagnóstico por imagemRESUMO
BACKGROUND: The possibility that a multi-host wildlife reservoir is responsible for maintaining transmission of Leishmania (Viannia) braziliensis causing human cutaneous and mucocutaneous leishmaniasis is tested by comparative analysis of infection progression and infectiousness to sandflies in rodent host species previously shown to have high natural infection prevalences in both sylvatic or/and peridomestic habitats in close proximity to humans in northeast Brazil. METHODS: The clinical and parasitological outcomes, and infectiousness to sandflies, were observed in 54 colonized animals of three species (18 Necromys lasiurus, 18 Nectomys squamipes and 18 Rattus rattus) experimentally infected with high (5.5 × 10(6)/ml) or low (2.8 × 10(5)/ml) dose L. (V.) braziliensis (MBOL/BR/2000/CPqAM95) inoculum. Clinical signs of infection were monitored daily. Whole animal xenodiagnoses were performed 6 months post inoculation using Lutzomyia longipalpis originating from flies caught in Passira, Pernambuco, after this parasite evaluation was performed at necropsy. Heterogeneities in Leishmania parasite loads were measured by quantitative PCR in ear skin, liver and spleen tissues. RESULTS: All three rodent species proved to establish infection characterized by short-term self-resolving skin lesions, located on ears and tail but not on footpads (one site of inoculation), and variable parasite loads detected in all three tissues with maximum burdens of 8.1 × 10(3) (skin), 2.8 × 10(3) (spleen), and 8.9 × 10(2) (liver). All three host species, 18/18 N. lasiurus, 10/18 N. squamipes and 6/18 R. rattus, also proved infectious to sandflies in cross-sectional study. R. rattus supported significantly lower tissue parasite loads compared to those in N. lasiurus and N. squamipes, and N. lasiurus appeared to be more infectious, on average, than either N. squamipes or R. rattus. CONCLUSIONS: A multi-host reservoir of cutaneous leishmaniasis is indicated in this region of Brazil, though with apparent differences in the competence between the rodent species. The results provide preliminary insights into links between sylvatic and peri-domestic transmission cycles associated with overlaps in the rodent species' ecological niches.
Assuntos
Reservatórios de Doenças , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/veterinária , Psychodidae/parasitologia , Ratos/parasitologia , Doenças dos Roedores/parasitologia , Sigmodontinae/parasitologia , Animais , Brasil/epidemiologia , Estudos Transversais , Transmissão de Doença Infecciosa , Feminino , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/transmissão , Masculino , Carga Parasitária , Doenças dos Roedores/patologia , Doenças dos Roedores/transmissãoRESUMO
BACKGROUND: Leishmania parasites cause leishmaniasis in humans and animals worldwide. These parasites are transmitted by phlebotomine sand flies, which become infected upon feeding on an infected mammalian host. We assessed the occurrence of Leishmania infection in small mammals in an area of cutaneous and visceral leishmaniasis endemicity. METHODS: A total of 180 small mammals were trapped in 2003 and 2006 in a rural area in north-eastern Brazil. Spleen and skin samples from these animals were assessed by two PCR protocols, one targeting Leishmania (Viannia) spp. and other Leishmania (Leishmania) infantum. Additionally, serum samples were tested by an immunochromatographic test with rK39 as antigen. RESULTS: Overall, 23.2% (38/164) of the animals were positive to L. (V.) spp. and 8.8% (14/160) to L. (L.) infantum). Five animals of four species (Didelphis albiventris, Nectomys squamipes, Rattus rattus and Holochilus sciureus) were positive by both PCR protocols, an overall co-infection rate of 2.5%. By serology, 5% (7/139) of the animals were positive, but all of them were PCR-negative. An isolate obtained from a water rat (N. squamipes) was characterized as L. (V.) braziliensis (zymodeme Z-74). CONCLUSIONS: This study reinforces the involvement of different small mammals (e.g., N. squamipes, R. rattus and H. scieurus) in the transmission cycles of L. (V.) braziliensis and L. (L.) infantum in north-eastern Brazil. The finding of L. (V.) braziliensis infection in black rats suggests a rapid process of adaptation of a New World Leishmania species to an Old World rodent and raises interesting questions regarding the co-evolution of these parasites and their vertebrate hosts.
Assuntos
Reservatórios de Doenças/veterinária , Leishmaniose/epidemiologia , Leishmaniose/transmissão , Psychodidae/parasitologia , Animais , Brasil/epidemiologia , Estudos Transversais , Reservatórios de Doenças/parasitologia , Feminino , Humanos , Leishmania/isolamento & purificação , Leishmania/patogenicidade , Masculino , Marsupiais/parasitologia , Gambás/parasitologia , Ratos , Roedores/parasitologia , Zoonoses/parasitologiaRESUMO
To expand the available panel of recombinant proteins that can be useful for identifying Leishmania-infected dogs and for diagnosing human visceral leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and genomic libraries by using pools of serum samples from infected dogs and humans. The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein 70, a kinesin, a polyubiquitin, and two novel hypothetical proteins. Histidine-tagged recombinant proteins were produced after subcloning these DNA fragments and evaluated by using an enzyme-linked immunosorbent assays with panels of canine and human serum samples. The enzyme-linked immunosorbent assays with different recombinant proteins had different sensitivities (67.4-93.0% and 36.4-97.2%) and specificities (76.1-100% and 90.4-97.3%) when tested with serum samples from Leishmania-infected dogs and human patients with VL. Overall, no single recombinant antigen was sufficient to serodiagnosis all canine or human VL cases.
Assuntos
Doenças do Cão/diagnóstico , Genes de Protozoários/genética , Leishmania infantum/genética , Leishmaniose Visceral/diagnóstico , Animais , Antígenos de Protozoários/genética , Clonagem Molecular , Doenças do Cão/parasitologia , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Proteínas de Choque Térmico HSP70/genética , Humanos , Cinesinas/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Poliubiquitina/genética , Proteínas Recombinantes/genética , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/veterináriaRESUMO
Este estudo tem como objetivo geral caracterizar a epidemiologia da leishmaniose tegumentar americana em unidade de treinamento militar, localizada no Estado de Pernambuco. Entre 2002 e 2003, vinte e três casos foram diagnosticados através de exame clínico, detecção do parasita e teste de intradermoarreação de Montenegro. Sete amostras de Leishmania (Viannia) braziliensis foram isoladas destes pacientes, identificadas através de reações com anticorpos monoclonais específicos e perfil eletroforético com isoenzimas. Um inquérito epidemiológico de prevalência da infecção por IDRM foi realizado na população que realizou treinamento neste período, no qual foi identificada uma prevalência de 25,3 por cento de infecção. Os dados obtidos, associados com achados prévios nesta área, apresentam evidências da manutenção de um ciclo enzoótico, com a ocorrência de surtos periódicos de leishmaniose tegumentar americana posteriormente à realização de treinamentos nas áreas de floresta Atlântica remanescente.
Assuntos
Humanos , Animais , Masculino , Anticorpos Antiprotozoários/imunologia , Surtos de Doenças , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/epidemiologia , Militares , Anticorpos Monoclonais/imunologia , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Testes Intradérmicos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Meglumina/uso terapêutico , Prevalência , ÁrvoresRESUMO
The aim of work was to study the epidemiology of American tegumentary leishmaniasis in a military training unit situated in Zona da Mata region of Pernambuco State. Between 2002 and 2003 twenty-three cases were notified by clinical exam, detection and/or isolation of parasite and Montenegro skin test. Seven stocks of Leishmania (Viannia) braziliensis were obtained from patients, identified by a panel of specific monoclonal antibodies and isoenzymatic electrophoresis profiles. An epidemiologic survey on prevalence of infection was carried out by Montenegro skin test in the population that underwent training activities during the same period, out of which 25.3% were identified as positive. These results in association with previous data from this area, shows the maintenance of a primary transmission cycle and the occurrence of periodical outbreaks after training activities in local areas of remnant Atlantic rain forest.
Assuntos
Surtos de Doenças , Leishmania braziliensis , Leishmaniose Cutânea/epidemiologia , Militares , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/análise , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Humanos , Testes Intradérmicos , Leishmania braziliensis/imunologia , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina , Compostos Organometálicos/uso terapêutico , Prevalência , ÁrvoresRESUMO
BACKGROUND: It is uncertain whether Leishmania parasites ever disappear after clinical cure of American cutaneous leishmaniasis (ACL). Recently, sensitive molecular techniques have allowed the identification of Leishmania parasites directly in specimens from patients' scars. METHODS: Scars of 32 patients from northeastern Brazil who were treated and clinically cured of ACL were analyzed by use of polymerase chain reaction (PCR), culture, and histopathologic examination. RESULTS: DNA specific for Leishmania (Viannia) was detected in scars of 30 (93.7%) of 32 patients. In specimens from 3 of the scars, Leishmania parasites could be isolated by culture; PCR results also were positive for those 3 specimens. No parasites were found by histopathologic examination, and fibrotic alterations were present in all cases, with slight inflammatory foci observed in 4 of the cases studied. CONCLUSIONS: The results suggest that clinical cure of ACL is rarely associated with sterile cure. The implications of persistence of parasites for the clinical evolution, relapse, and transmission of leishmaniasis deserves further studies, particularly with the increasing incidence of coinfection with leishmaniasis and acquired immunodeficiency syndrome.
Assuntos
Cicatriz/parasitologia , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Adolescente , Adulto , Animais , Cicatriz/patologia , DNA de Protozoário/análise , Feminino , Humanos , Leishmaniose Cutânea/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
American cutaneous leishmaniasis (ACL) has been increasing in Pernambuco, thus becoming an important problem for Public Health. The incindence is predominant in the region called "Zona da Mata", in the east of this state. This region corresponds geographically to the primitive area of the Atlantic forest. In order to characterize the eco-epidemiology expression of ACL in this region, two localities situated in the municipalities of Amaraji e Cortes have been selected by the criterion of higher incindence of human cases. Five stocks of patients were characterized and identified on the basis of enzyme profiles as a new variant of Leishmania (V.) braziliensis. A survey of wild and domestic animals was carried out by means of a parasitological and serological diagnosis. Through the analysis of the spleen and liver imprints, were detected amastigotes compatible with Leishmania in five Nectomys s. squamipes, five Bolomys l. pixuna, two Rattus r. alexandrinus and one Rattus r. frugivorus. For two years we carried out monthly sandflies captures using CDC light traps as well as manual captures. Lutzomyia whitmani was predominant, which accounted for 97.4 por cento of the total. These data indicate a strong evidence on the vector and the potential reservoirs of L. braziliensis in this region.