Parasite species variation and impact of spatial displacement of the population on cutaneous leishmaniasis in Rio de Janeiro, Brazil.

BACKGROUND: Cutaneous leishmaniasis results from complex interactions between human beings, vectors and the environment. Parasitic species differ in epidemiological and geographical contexts. METHODS: We studied a retrospective cohort of 696 patients with cutaneous leishmaniasis treated at a reference centre in the state of Rio de Janeiro, Brazil, between 2000 and 2015. We analysed displacements due to work, leisure and migrations with identification of Leishmania species. RESULTS: The geographic distribution of autochthonous cases showed that >95% of infections occurred in urban areas. In the state of Rio de Janeiro, most cases were concentrated in the cities surrounding forest parks and nature conservation areas. The same applies to the city of Rio de Janeiro, where these infections occurred in the neighbourhoods surrounding some mountain and forest areas. The non-displacement group included 575 (82.6%) patients and the displacement group included 121 (17.4%) patients. Leishmania (Viannia) braziliensis predominated in both groups. Other species were found in the displacement group. CONCLUSIONS: The disordered urbanization of the state of Rio de Janeiro in recent decades has created conditions for the emergence of urban foci of transmission close to forest areas. Changes in the environment, movement of infected individuals and adaptation of sandflies may have contributed to this.

Clinical features and therapeutic response in adult and pediatric patients with American tegumentary leishmaniasis in Rio de Janeiro.

BACKGROUND: American tegumentary leishmaniasis (ATL) is a neglected disease with wide territorial distribution. Knowledge is scarce in children and adolescents. This study aims to compare the clinical features and response to antimony treatment in pediatric and adult patients with cutaneous leishmaniasis. METHODS: A retrospective cohort study was performed with 659 patients who attended a reference centre in Rio de Janeiro, Brazil, from 2000 to 2015. The pediatric cohort consisted of 131 (20%) patients and the adult cohort consisted of 528 (80%) patients. RESULTS: The epidemiological profile, antimony therapeutic response and incidence of adverse events (AE) were different in the pediatric cohort compared with the adult cohort. Mucosal form was less frequent in the pediatric cohort (RR:0.49, p=0.011). Lesions in the head, neck and trunk were more frequent in the pediatric cohort (RR:1.49, p=0.043). The effectiveness of antimony treatment was superior in the pediatric cohort (88.3% vs 76.6%) with a shorter healing time (RR:0.49, p=0.009). Pediatric patients had lower proportions of moderate to severe AE compared with adults (RR:0.45, p=0.027). Clinical AE predominated in the adult cohort (RR:0.40, p=0.000) and laboratory AE in the pediatric cohort (RR:1.50, p=0.023). CONCLUSIONS: This study adds to the body of knowledge on differences that exist between different age groups in ATL.

Is There Any Difference between the In Situ and Systemic IL-10 and IFN-γ Production when Clinical Forms of Cutaneous Sporotrichosis Are Compared?

Fungus of the Sporothrix schenckii complex can produce skin lesions in humans, commonly lymphocutaneous (LC) and fixed (F) forms of sporotrichosis. Some authors have suggested that clinical forms are influenced by differences in virulence and genetic profile of isolates. But little is known about the role of immune response in determining the clinical outcome of sporotrichosis. To verify the profile of systemic and in situ IFN-γ and IL-10 expression in sporotrichosis patients, and consequently to detect any difference between the two compartments and/or clinical presentation, we quantified the number of IFN-γ and IL-10 producer peripheral blood mononuclear cells stimulated with S. schenckii antigen (Ss-Ag) by Elispot, and quantified cytokines expression by in situ immunohistochemistry in the same patient. Three groups were formed: 1- LC (n = 9); 2- F (n = 10); 3- healthy individuals (n = 14). All sporotrichosis patients produced high amounts of systemic IFN- γ when compared to uninfected individuals. No differences were observed between LC and F groups. Regarding in situ IL-10 expression, a difference between LC and F groups was observed: LC lesions presented higher amounts of IL-10 than F lesions differently from systemic IL-10 which showed similarities. Our data suggests that LC lesions present higher IL-10 expression which could be related to regulatory mechanisms for compensating the tissue injury, however favoring fungal persistence in the lesions. Surprisingly, there were no differences in systemic and in situ IFN- γ expression between CL and F patients, although it was significantly higher expressed in these patients than in healthy individuals.

Avaliação vestibular de crianças e adolescentes com tontura / Analysis of vestibular system in children and teenagers with vertigo

Objetivo: Descrever as características clínicas da vestibulopatia e os fatores a ela associados, a partir dos resultados da vectoeletronistagmografia (VENG) na população pediátrica referida para avaliação no Setor de Otoneurologia de um Hospital Universitário. Métodos: Estudo observacional, descritivo, transversal, com coleta retrospectiva de dados de fichas do Setor de Otoneurologia de um Hospital Universitário, contendo a anamnese otoneurológica e os resultados de VENG realizados em crianças e adolescentes com tontura, durante o período de maio de 1998 a dezembro de 2010. Resultados: Foram avaliadas 16 pacientes, com idade entre quatro e 18 anos, com distribuição igualitária de gênero. A maioria apresentava tontura rotatória, acompanhada de zumbido e de náuseas ou vômitos, sem alteração à VENG. A história de traumatismo craniano foi o único fator significativamente associado à presença de alteração à VENG, estando presente nos três pacientes que apresentaram resultados compatíveis com síndrome vestibular periférica. Conclusão: A sintomatologia vestibular periférica predomina na infância. Ainda assim, na maioria das vezes a VENG se apresenta normal, o que sugere uma limitação diagnóstica deste exame. No entanto, quando a sintomatologia vestibular persistente ocorre após quadro de traumatismo craniano, a VENG não só é útil à diferenciação de afecções periféricas de centrais, como auxilia a conduta terapêutica a ser tomada. (AU)

Objective: To describe the clinical features of vestibular disease and factors associated with it, based on the results of vectoelectronystagmography (VENG) in the pediatric population evaluated at the Otoneurology of an University Hospital. Methods: This observational, descriptive, cross-sectional study, with retrospective data collection of registration forms of Otoneurology Department of a University Hospital, containing otoneurologic interviews and the results of VENG, was performed in children and adolescents with dizziness from May 1998 to December 2010. Results: Sixteen patients 4-18 years old were evaluated, with equal gender distribution. Most patients had vertigo accompanied by tinnitus and nausea or vomiting, without changing the VENG. A history of brain damage was the only factor significantly associated with the presence of alterations in the VENG, which was observed in three patients who showed consistent results with peripheral vestibular syndrome. Conclusion: The peripheral vestibular symptomatology predominates in childhood. However, most cases the VENG seems to be normal, which suggests a limitation of this diagnostic testing. But, when persistent vestibular symptoms occur after the episode of brain trauma, VENG is useful to differentiate peripheral from central disorders, and helps in the therapeutic conduct to be adopted. (AU)

Apoptosis and frequency of total and effector CD8+ T lymphocytes from cutaneous leishmaniasis patients during antimonial therapy.

BACKGROUND: Leishmaniasis is an important parasitic disease affecting millions worldwide. Human cutaneous leishmaniasis (CL) is endemic in Rio de Janeiro, Brazil, where is caused by Leishmania braziliensis. The adaptive immune response is accountable for the healing of CL and despite of key role of CD8+ T cells in this immune response little is known about the CD8+ T lymphocytes frequencies, apoptosis and antigen-responsive CD8+ T lymphocytes of CL patients during antimonial therapy. METHODS: Using flow cytometry, we examined total and effector CD8+ T cells from CL patients before (PBT), during (PDT) and after (PAT) treatment for apoptosis and frequencies upon isolation and after in vitro L. braziliensis antigens (LbAg)-stimulation culture. Besides, a correlation study between immunological findings and lesion size was done. RESULTS: PDT showed lower frequencies of total CD8+ T lymphocytes and higher levels of apoptosis of these cells, which were also observed following LbAg-stimulation culture. Regarding effector CD8+ T cells, high frequencies were observed in PDT, while lower frequencies were observed in PAT. Interestingly, PDT showed higher frequencies of apoptotic-effector CD8+ T lymphocytes. Similar results were seen after in vitro antigenic-stimulation assays. Correlation analysis showed that the greater the size of lesion, the smaller the frequency of effector CD8+ T lymphocytes in PDT and PAT, as well as a positive correlation between apoptotic-effector CD8+ T cells frequency and lesion size of PDT. CONCLUSIONS: Changes in effector CD8+ T-lymphocyte frequencies, during and after treatment, seem to represent a critical stage to generate an efficient immune response and suggest that these cells would be evolved in the triggering or in the resolution of lesion, under the influence of therapy. This hypothesis opens new perspectives to clarify controversial statements about the protective or deleterious role of CD8+ T cells in the cure or aggravation of CL and the new approach of evaluating patients during treatment proved to be of utmost importance for understanding the immune response in the healing process of human CL.

American tegumentary leishmaniasis caused by Leishmania (Viannia) braziliensis: assessment of parasite genetic variability at intra- and inter-patient levels.

BACKGROUND: The genetic variability of Leishmania (Viannia) braziliensis was assessed at intra and interpatient levels of individuals with different clinical manifestations of American tegumentary leishmaniasis (ATL). METHODS: Fifty-two samples, of which 13 originated from cutaneous lesions and 39 from mucosal lesions, provided by 35 patients, were examined by low-stringency single-specific-primer PCR (LSSP-PCR) and phenetic analysis. Genetic variability of L. (V.) braziliensis, in kinetoplast DNA (kDNA) signatures, was compared both from different patients and from different lesions of the same patient. Phenetic analysis was performed to evaluate the degree of heterogeneity of the kDNA minicircles. In order to evaluate inter and intrapatient L. (V.) braziliensis genetic variability, the percentage of shared bands and analysis of the coefficients of similarity were analyzed. RESULTS: Different genetic profiles, representing kDNA signatures of the parasite, were obtained by LSSP-PCR analysis of each sample. Phenetic analysis grouped genetic profiles of different levels of differentiation from more similar to most divergent. The percentage of shared bands at the inter and intrapatient levels was 77% and 89%, respectively. Comparison of the average inter and intrapatient coefficients of similarity and their standard deviations were statistically significant (p < 0.001). CONCLUSION: Genetic variability at the intrapatient level was less pronounced than that between different patients. A conceptual model was proposed to better understand the complexity at both levels.

Endemic tegumentary leishmaniasis in Brazil: correlation between level of endemicity and number of cases of mucosal disease.

The purpose of this study was to establish a correlation between the endemic level of tegumentary leishmaniasis in different regions of Brazil during 2002-2009 and the number of cases of mucosal or mucocutaneous leishmaniasis. The proportion of mucosal leishmaniasis was inversely correlated with prevalence of infection. In areas with a lower infection prevalence, the proportion of mucosal leishmaniasis increased (P < 0.05). The hypothesis of an Amazonian origin and dissemination through human migration is considered. Our results show that in regions with lower prevalence and endemically younger, the proportion of cases that evolve to the mucosal form is higher than in regions with higher prevalence and endemically older.