Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis.

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

Oral and oropharyngeal mucosal lesions: clinical-epidemiological study of patients attended at a reference center for infectious diseases.

OBJECTIVE: To determine the prevalence, epidemiological profile, and clinical characteristics of Oral or Oropharyngeal Mucosal Lesions (OOPML) in patients attended at the Otorhinolaryngology Service of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ) from 2005 to 2017. METHODS: Statistical analysis of descriptive data from medical records (gender, age, education level, skin color, origin, smoking, alcoholism, HIV co-infection, time of disease evolution, first symptom, and OOPML location) was performed. RESULTS: Of 7551 patients attended at the service, 620 (8.2%) were included in the study. OOPML were classified into developmental anomalies (n = 3), infectious diseases (non-granulomatous n = 220; granulomatous n = 155), autoimmune diseases (n = 24), neoplasms (benign n = 13; malignant, n = 103), and unclassified epithelial/soft tissue diseases (n = 102). OOPML of infectious diseases (60.5%) and neoplasms (18.7%) were the most frequent. The predominant demographics of patients with OOPML were: males (63.5%), white (53.5%), and those in the fifth to sixth decades of life (43.3%). Local pain (18.1%) and odynophagia (15%) were the most reported first symptoms, and the most frequent OOPML sites were the palatine tonsil (28.5%), hard palate (22.7%), and tongue (20.3%). The median evolution time was three months. CONCLUSIONS: Infectious OOPML were the most frequent, as expected in a reference center for infectious diseases, and thus, they are likely to be less frequent in general care and/or dental services. Underreporting of OOPML is possible, as oral/oropharyngeal examination is often not included in the routine medical examination. Oral cavity/oropharynx examination should be performed by specialists, such as dentists and otorhinolaryngologists, who have the expertise in identifying OOPML, even in incipient/asymptomatic cases. Given the numerous diseases in which OOPML can present, diagnosis could be facilitated by multidisciplinary teams, potentially enabling the early treatment of diseases, and thus, reduce morbidity and improve prognosis. The use of standardized medical records for oral/oropharyngeal systematic examination could provide relevant tools for differential diagnoses and information for new clinical-epidemiological studies. LEVEL OF EVIDENCE: Level 3.

Oral and oropharyngeal mucosal lesions: clinical-epidemiological study of patients attended at a reference center for infectious diseases

Abstract Objective To determine the prevalence, epidemiological profile, and clinical characteristics of Oral or Oropharyngeal Mucosal Lesions (OOPML) in patients attended at the Otorhinolaryngology Service of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ) from 2005 to 2017. Methods Statistical analysis of descriptive data from medical records (gender, age, education level, skin color, origin, smoking, alcoholism, HIV co-infection, time of disease evolution, first symptom, and OOPML location) was performed. Results Of 7551 patients attended at the service, 620 (8.2%) were included in the study. OOPML were classified into developmental anomalies (n = 3), infectious diseases (non-granulomatous n = 220; granulomatous n = 155), autoimmune diseases (n = 24), neoplasms (benign n = 13; malignant, n = 103), and unclassified epithelial/soft tissue diseases (n = 102). OOPML of infectious diseases (60.5%) and neoplasms (18.7%) were the most frequent. The predominant demographics of patients with OOPML were: males (63.5%), white (53.5%), and those in the fifth to sixth decades of life (43.3%). Local pain (18.1%) and odynophagia (15%) were the most reported first symptoms, and the most frequent OOPML sites were the palatine tonsil (28.5%), hard palate (22.7%), and tongue (20.3%). The median evolution time was three months. Conclusions Infectious OOPML were the most frequent, as expected in a reference center for infectious diseases, and thus, they are likely to be less frequent in general care and/or dental services. Underreporting of OOPML is possible, as oral/oropharyngeal examination is often not included in the routine medical examination. Oral cavity/oropharynx examination should be performed by specialists, such as dentists and otorhinolaryngologists, who have the expertise in identifying OOPML, even in incipient/asymptomatic cases. Given the numerous diseases in which OOPML can present, diagnosis could be facilitated by multidisciplinary teams, potentially enabling the early treatment of diseases, and thus, reduce morbidity and improve prognosis. The use of standardized medical records for oral/oropharyngeal systematic examination could provide relevant tools for differential diagnoses and information for new clinical-epidemiological studies. Level of evidence: Level 3.

First report of Leishmania RNA virus 1 in Leishmania (Viannia) braziliensis clinical isolates from Rio de Janeiro State - Brazil

BACKGROUND Leishmania parasites carry a double-stranded RNA virus (Leishmania RNA virus - LRV) that has been divided in LRV1 and LRV2. OBJECTIVES Leishmania (Viannia) braziliensis clinical isolates were assessed in order to determine LRV presence. METHODS Two-round polymerase chain reaction (PCR and nested PCR) was performed to detect LRV1 or LRV2 in L. (V.) braziliensis clinical isolates (n = 12). FINDINGS LRV1 was detected in three clinical isolates which was phylogenetically related to other sequences reported from other American tegumentary leishmaniasis (ATL) endemic areas of Brazil. Patients infected with L. (V.) braziliensis LRV-negative showed only cutaneous lesions while LRV-positive reported different manifestations. MAIN CONCLUSION Data presented here show for the first time that LRV1 is circulating in L. (V.) braziliensis clinical isolates from Rio de Janeiro State in Brazil.

Parasite load, iNOS and cytokine profiles, and histopathological aspects of Leishmania infantum infection in dogs with different clinical presentations / Carga Parasitária, iNOS, citocinas e histopatologia na infecção por Leishmania infantum em cães com apresentações clínicas distintas

ABSTRACT: Visceral leishmaniasis (VL) is a zoonotic disease with a canine urban reservoir in South America. Dogs from an endemic area within Brazil, which were naturally infected with Leishmania infantum, and those presenting severe clinical (SC), mild, or no clinical (MNC) disease, were evaluated. Parasite load, histopathology, and cytokine and iNOS mRNA expressions were assessed in the spleen and liver in order to determine the potential markers for disease susceptibility or resistance. As a result, dogs with both SC and MNC had high parasite loads; IFN-γ was the most expressive cytokine in both organs, along with IL-6 and IL-4 being detected in the spleen and liver, and IL-10 only in liver. The hepatic tissue presented higher medians for IFN-γ and IL-10, and was the main organ to produce cytokines with hepatic IL-10 suggesting a regulatory follow up. Granulomas were detected in both organs; however, when absent in spleen, they were associated with elevated IL-6 levels, thus highlighting the anti-inflammatory role of IL-6. Microscopic lesions in the spleen were predominantly characterized by an extensively disorganized white pulp and splenic response was suggested as sub optimized. Parasite load, tissue damage, and immunological response may vary in the dogs with similar clinical symptoms, which may not be a good parameter for assessing the animal's susceptibility to VL.

RESUMO: A Leishmaniose visceral (LV) é uma doença zoonótica com reservatório canino na América do Sul. Cães oriundos de área endemica brasileira, naturalmente infectados por Leishmania infantum, apresentando doença clínica severa (CS) ou doença branda ou ausente (BA) foram avaliados. Carga parasitária, histopatologia e expressão de mRNA de citocinas e iNOS foram analisados em baço e fígado, buscando determinar possíveis marcadores de susceptibilidade ou resistência à doença. Como principais resultados, tanto cães CS como BA apresentaram alta carga parsitária. IFN-γ foi a citocina mais expressiva em ambos os órgãos, sendo IL-6 e IL-4 também detectadas em baço e fígado e IL-10 em fígado. No tecido hepático foram encontradas as maiores medianas de IFN-γ e IL-10, sendo o fígado o principal órgão produtor de citocinas, com IL-10 sugerindo acompanhamento regulatório. Granulomas foram detectados em ambos os órgãos. Quando de sua ausência no baço, essa foi associada à elevação dos níveis de IL-6, salientando o papel anti-inflamatório dessa citocina. Alterações microscópicas foram principalmente caracterizadas por extensiva desorganização de polpa branca, com a resposta esplência sendo sugerida como subotimizada. Carga parasitária, dano tecidual e resposta immune variaram mesmo em cães com quadros clínicos similares, não sendo, portanto, a análise clínica um bom parâmetro para avaliação de susceptibilidade animal à LV.

Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary leishmaniasis acquired in different Brazilian regions

Abstract INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.

Perfil epidemiológico y molecular de Rickettsiosis en localidades de frontera peruana / Epidemiological and molecular profile of Rickettsiosis in peruvian border locations

RESUMEN Objetivos. Determinar circulación de rickettsias durante los años 2010 al 2011 en localidades fronterizas de cuatroregiones del Perú, y sus características clínicas epidemiológicas y moleculares. Materiales y métodos. Estudio transversal realizado en Tumbes, Tacna, Madre de Dios y Loreto. Se obtuvo datos clínicos epidemiológicos y muestras de sangre total para cultivo y para ensayo de inmunofluorescencia indirecta (IFI). Fue utilizado ADN extraído de cultivos de leucocitos y de ectoparásitos, aquellos genes específicos para rickettsias que amplificaron exitosamente fueron secuenciados y analizados. Resultados. El 33,8% de los encuestados portaba anticuerpos a rickettsias; en Loreto 21,7%, en Madre de Dios 33,0%, en Tacna 48,2% y en Tumbes 33,3%, encontrándose seropositividad en más del 40% de aislamientos confirmados por IFI. Las pruebas moleculares evidenciaron la presencia de Rickettsia felis en Ctenocephalides felis de perros y gatos de Tacna y una especie recientemente reportada para Latinoamérica: Candidatus Rickettsia asemboensis en pulgas Ctenocephalides felis de gatos y perros de Loreto y Madre de Dios. De la población estudiada, el 81,4% informó antecedentes de contacto con ectoparásitos, el 22,6% eran asintomáticos y el 27,8% habitaban viviendas sin agua ni desagüe, con piso de tierra. Conclusiones. Evidencias serológicas y moleculares confirman la circulación de rickettsias en las localidades fronterizas estudiadas, con predisponentes epidemiológicos, demostrándose presencia de dos especies: Rickettsia felis y Candidatus Rickettsia asemboensis, las que representarían una amenaza potencial para la salud de los pobladores.

ABSTRACT Objectives. To determine the circulation of Rickettsia in the years 2010 and 2011 in border locations in four regions ofPeru and their clinical epidemiological and molecular characteristics. Materials and Methods. A cross-sectional study was carried out in Tumbes, Tacna, Madre de Dios, and Loreto. Whole blood samples were obtained from participants for culture and indirect immunofluorescence (IIF) testing. The DNA taken from leukocytes and ectoparasite cultures was used, and those genes detected for Rickettsia that were successfully amplified were sequenced and analyzed. Results. A total of 33.8% of those surveyed carried Rickettsia antibodies (21.7% in Loreto, 33.0% in Madre de Dios, 48.2% in Tacna, and 33.3% in Tumbes). Seropositivity was confirmed with IIF in over 40% of isolates. Molecular tests showed the presence of Rickettsia felis in Ctenocephalides felis of dogs and cats in Tacna and a recently reported species for Latin America, Candidatus Rickettsia asemboensis, in fleas of cats and dogs in Loreto, Madre de Dios, and Tacna. Of the population studied, 81.4% reported a history of contact with ectoparasites, 22.6% were asymptomatic, and 27.8% lived in earthen-floored homes without water or drainage. Conclusions. Serological and molecular evidence confirms the circulation of Rickettsia in the border locations studied, with predisposing epidemiological factors. Tests confirm the presence of two species, Rickettsia felis and Candidatus Rickettsia asemboensis, which represent a potential threat to the health of the inhabitants.

Sporotrichoid leishmaniasis: a cross-sectional clinical, epidemiological and laboratory study in Rio de Janeiro State, Brazil

ABSTRACT Background Atypical presentations of cutaneous leishmaniasis include sporotrichoid leishmaniasis (SL), which is clinically described as a primary ulcer combined with lymphangitis and nodules and/or ulcerated lesions along its pathway. Aims To assess the differences between patients with sporotrichoid leishmaniasis and typical cutaneous leishmaniasis (CL). Methods From January 2004 to December 2010, 23 cases of SL (4.7%) were detected among 494 CL patients diagnosed at a reference center for the disease in Rio de Janeiro State, Brazil. These 23 cases were compared with the remaining 471 patients presenting CL. Results SL predominated in female patients (60.9%, p = 0.024), with older age (p = 0.032) and with lesions in upper limbs (52.2%, p = 0.028). CL affected more men (64.5%), at younger age, and with a higher number of lesions exclusively in lower limbs (34.8%). Conclusions Differences in clinical and epidemiological presentation were found between SL patients as compared to CL ones, in a region with a known predominance of Leishmania (Viannia) braziliensis. The results are similar to the features of most of the sporotrichosis patients as described in literature, making the differential diagnosis between ATL and sporotrichosis more important in overlapping areas for both diseases, like in Rio de Janeiro State.

Leishmanioses do continente americano / Leishmaniasis in the Americas

No Brasil, ela já foi responsável por epidemias em diferentes cidades. Nos últimos dez anos, sua letalidade aumentou em diversas regiões do país. Em várias partes do mundo ela vem se expandindo, inclusive em lugares onde, anteriormente, não havia registro de transmissão. A infecção por parasitos do gênero Leishmania causa uma das doenças tropicais mais negligenciadas da atualidade. Estima-se que existam 350 milhões de pessoas em risco de contrair a infecção, sobretudo nas áreas mais pobres do planeta, e que dois milhões de novos casos de leishmanioses ocorram a cada ano. Esse grave cenário justifica o esforço empreendido pelos organizadores e demais pesquisadores do Instituto Oswaldo Cruz (IOC/Fiocruz) especialistas no assunto, assim como por profissionais de outras unidades da Fiocruz e instituições brasileiras: eles prepararam uma coletânea que compila o conhecimento já existente sobre o assunto, identifica os principais desafios e discute estratégias para enfrentá-los...

A questão do controle das leishmanioses no Brasil / The issue of control of leishmaniasis in Brazil

O controle de endemia de ocorrência nacional, atingindo regiões de características diferentes, embora implique principalmente o conhecimento de suas formas de transmissão nos diferentes contextos, além de frequência, distribuição e outros aspectos ecoepidemiológicos pertinentes, requer também informações que vão desde as manifestações clínicas e os diagnósticos de suspeição e confirmatórios, ao acesso à atenção e resposta à terapêutica. Apesar da abordagem delicada ou difícil das leishmanioses, sob qualquer desses aspectos, a complexidade do controle destaca-se pela grande multiplicidade de elementos envolvidos na transmissão e a consequente produção de infecção e doença. (AU)

Histoplasmose cutânea primária: relato de caso em paciente imunocompetente e revisão de literatura / Primary cutaneous histoplasmosis: case report on an immunocompetent patient and review of the literature

É relatado um caso de histoplasmose cutânea primária em um homem de 45 anos, com apresentação de um nódulo eritematoso no dorso da mão direita acompanhado de linfadenomegalia regional indolor, que se desenvolveu após trauma local ocorrido durante treinamento militar em túnel habitado por morcegos. O exame histológico de biópsia da lesão cutânea mostrou um infiltrado granulomatoso, porém não evidenciou elementos fúngicos. O cultivo deste material incubado em Ágar Sabouraud mostrou crescimento de Histoplasma capsulatum. Não foi encontrada evidência de envolvimento sistêmico ou imunossupressão. O tratamento com 400mg diários de itraconazol oral durante 6 meses resultou na remissão completa da lesão, mantida um ano após o término do tratamento.

This report describes a case of primary cutaneous histoplasmosis in a 45-year-old male. The presentation consisted of an erythematous nodule on the back of the right hand, accompanied by nontender regional lymphadenomegaly that developed following local trauma that occurred during military training in a tunnel inhabited by bats. Histological examination of a biopsy specimen from the skin lesion showed granulomatous infiltrate, but did not show fungal elements. Culturing of this material, incubated in Sabouraud agar, showed growth of Histoplasma capsulatum. No evidence of systemic involvement or immunosuppression was found. Treatment with 400 mg/day of itraconazole orally for six months resulted in complete remission of the lesion, which was maintained one year after the end of the treatment.

Sistema imunológico: atualidades e perspectivas para a prática clínica / Immune system: present time and perspectives for clinical practice

O sistema imunológico (SI), à semelhança do sistema nervoso, tem uma participação central na biologia do Homo sapiens sapiens (sic), tendo na comunicação um dos esteios para sua organização e funcionamento. Além de ser capaz de distinguir o que é próprio (self) do que é não-próprio (non-self), o SI estrutura-se em rede, processando informações de modo a permitir o aprendizado e o desenvolvimento da memória, aspectos fundamentais para a relação do organismo com o meio ambiente, com importantes implicações no adoecimento humano. Com base nestas considerações, objetiva-se, no presente manuscrito, apresentar, de modo sintético, os principais aspectos do sistema imunológico.

The immune system (IS), like the nervous system, plays a central role in the biology of Homo sapiens sapiens (sic), eith communication as a base for its organization and operation. In addition to an ability to distinguish self from non-self, the IS structures itself in a network, processing information in a way to allow learning and the development of memory, fundamental aspects in the organim's relation with the environment, with important implications in human illnesses. Based on these considerations, this review aims to present, in a synthetic manner, the principal aspects of the immune system.