Comparative assessment of skin reactivity to thimerosal- or phenol-preserved Imunoleish® antigen in dogs with suspected American Tegumentary Leishmaniasis in an endemic area of the state of Rio de Janeiro, Brazil

The leishmanin skin test (LST), which is an in vivo test that assesses the cellular immune responses to Leishmania-derived antigens, is an important tool in the laboratory diagnosis of American tegumentary leishmaniasis (ATL). This study aimed to compare the results obtained in LST employing the Imunoleish® antigen preserved with thimerosal (AgT) or phenol (AgP) and serological techniques to detect a possible infection caused by Leishmania (Viannia) braziliensis in dogs. The study included 172 dogs from an area endemic for ATL in the municipality of Paracambi, state of Rio de Janeiro, Brazil. The results obtained with Imunoleish® antigen preserved with thimerosal (AgT) or phenol (AgP) and serological tests were compared. Each dog received, intradermally, 0.1 mL of each antigen on the inner side of the right (AgT) and left (AgP) thighs. Five (2.7%) dogs presented ATL lesions. Of these, two were reactive to both formulations and three were reactive only to AgT. Among the 172 dogs, 68 (39.5%) were reactive only to AgT, 16 (9.3%)  only to AgP, and 11 (6.4%) to both formulations. Twenty-one (12.2%) sera samples were reactive by immunofluorescent antibody test (IFAT) and 21 enzyme-linked immunosorbent assay (ELISA). However, in only two dogs out of the five which Leishmania was isolated from, serological tests were positive. The LST and serological tests could be a useful tool in the diagnosis of L. (V.) braziliensis infection in dogs. Standardization of the techniques and reagents used could allow comparative studies on sensitivity, specificity, and positive and negative predictive values in dogs from different regions.Keywords: American Tegumentary Leishmaniasis, Leishmanin skin test, Diagnosis, Dogs, Host

Fatores associados à adesão a diferentes esquemas de tratamento com antimoniato de meglumina em ensaio clínico para leishmaniose cutânea

O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods

Prevalence of canine infection from endemic areas of American cutaneous leishmaniasis in Paracambi District, Rio de Janeiro State, between 1992 and 1993

Submitted by Sandra Infurna ([email protected]) on 2019-12-10T17:58:49Z No. of bitstreams: 1 RaquelSilva_Pacheco_etal_IOC_2005.pdf: 71014 bytes, checksum: eb2d10af0fb715b86f1eee2c20f2cd35 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-12-10T18:13:06Z (GMT) No. of bitstreams: 1 RaquelSilva_Pacheco_etal_IOC_2005.pdf: 71014 bytes, checksum: eb2d10af0fb715b86f1eee2c20f2cd35 (MD5)Made available in DSpace on 2019-12-10T18:13:06Z (GMT). No. of bitstreams: 1 RaquelSilva_Pacheco_etal_IOC_2005.pdf: 71014 bytes, checksum: eb2d10af0fb715b86f1eee2c20f2cd35 (MD5) Previous issue date: 2005Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Zoonoses. Rio de Janeiro, RJ, Brasil.Universidade Federal Rural do Rio de Janeiro. Instituto de Veterinária. Departamento de Saúde Pública. Seropédica, RJ, Brasil.Secretaria Municipal de Saúde do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia e Bioquímica Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Serviço de Patologia. Rio de Janeiro, RJ, Brasil.Instituto Superior de Tecnologia/FAETEC - Paracambi. Paracambim RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Departamento de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Secretaria Municipal de Saúde do Rio de Janeiro. Rio de Janeiro, RJ, Brasil.No município de Paracambi, Estado do Rio de Janeiro, foi realizado um inquérito epidemiológico sobre a leishmaniose tegumentar americana na população canina residente em áreas endêmicas rural e semiurbana. Foram cadastrados 179 cães e 138 (77,1%) foram examinados, segundo seus aspectos clínicos e desenvolvimento de hipersensibilidade tardia ao antígeno Imunoleish® e respostas sorológicas à reação de imunofluorescência indireta e ao ensaio imunoenzimático. Dos 9 (6,5.%) animais portadores de lesões/cicatrizes suspeitas, 66,7% foram causadas por Leishmania sp; 44,4% produziram infecção em hamsters e apresentaram crescimento em meio de cultura, compatíveis com o comportamento de Leishmania do complexo braziliensis. A caracterização molecular (análises isoenzimáticas e do perfil de restrição do KDNA) identificou 2 amostras como similares à Leishmania (Viannia) braziliensis. A prevalência da infecção canina observada através do teste cutâneo, RIFI e ELISA foi, respectivamente, 10,1%, 16,7% e 27,8%. A presença das formas clínica/subclínica da LTA na população canina associada à infecção humana sugere que o cão pode atuar como possível fonte de infecção, assim como na disseminação da doença.In the district of Paracambi, State of Rio de Janeiro an epidemiological survey for American tegumentary leishmaniasis in canine population was carried out in endemic localities. A total of 179 dogs was registered and 138 (77.1%) examined for their clinical aspects, development of delayed hypersensitivity (DHS) with Imunoleish® antigen and serological responses by indirect immunofluorescent reaction and enzyme-linked immunosorbent assay. In 9 (6.5%) dogs with active cutaneous lesions or suspect scars, 66.7% were caused by Leishmania sp; 44.4% produced infection in hamsters and showed growth in culture media, which was considered to be compatible with the species of Leishmania braziliensis complex. The molecular characterization (isoenzyme and KDNA restriction profiles) defined two strains with similar profiles for L. (Viannia) braziliensis. The prevalence of canine infection estimated by the cutaneous test, IFR and ELISA was 10.1%, 16.7% and 27.8%, respectively. The presence of clinical / sub-clinical form of ATL in canine population associated with human infections suggested that the dog can act as source of infection as well as for dissemination of the disease

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil

<div><p>Background</p><p>Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute.</p><p>Methods</p><p>A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of <i>Leishmania (Viannia) braziliensis</i> transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: <a href="https://clinicaltrials.gov/ct2/show/NCT01301924" target="_blank">NCT01301924</a>.</p><p>Results</p><p>Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7–29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1–31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony.</p><p>Conclusions</p><p>Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.</p></div

Subgroup analysis: Forest plot of absolute risk difference (RD) and relative risk (RR) with two-sided 95% confidence interval (CI) for major adverse events according to low versus high dose antimony treatment.

<p>Squares located to the right of the vertical solid line favor more major adverse events in the high dose antimony group.</p

Different stages of the wound healing process in American cutaneous leishmaniasis.

<p>Different stages of the wound healing process in American cutaneous leishmaniasis.</p

Baseline demographic and clinical characteristics of the modified intention-to-treat population.

<p>Baseline demographic and clinical characteristics of the modified intention-to-treat population.</p

Bubble plot of -log10(Raw p-value) by risk difference with a two-sided 95% confidence interval sized by number of subjects with adverse events in high dose versus low dose antimony groups.

<p>Note: Grey zone area corresponds to area of p-value<0.05; X stands for point estimates; point estimates within the grey zone area have p-values<0.05; circles are sized by the number of patients with adverse events; circles located to the right of the vertical solid line favor more adverse events in the high dose antimony group.</p