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1.
Rev. cuba. pediatr ; 92(3): e771, jul.-set. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1126765

ABSTRACT

Introducción: La leishmaniosis visceral es la más grave de las formas clínicas de la leishmaniosis, afecta principalmente a los niños y es potencialmente fatal. Objetivo: Exponer la caracterización clínico-epidemiológica de la leishmaniosis visceral en población pediátrica y su respuesta terapéutica. Métodos: Se realizó un estudio retrospectivo, longitudinal y descriptivo en el Hospital Italiano, Ciudad de Djibouti en el período septiembre 2016-agosto 2017. El universo lo conformaron 166 menores de 15 años que ingresaron con diagnóstico de fiebre prolongada sin foco de localización, la muestra fue de 22 niños con diagnóstico confirmado de leishmaniosis visceral. La información se obtuvo de las historias clínicas. Se operacionalizaron 20 variables: sociodemográficas, clínicas, analíticas, terapéuticas y evolutivas. Se utilizó el procesador Epidat 3.1. Los resultados se expresaron en valores absolutos y porcentajes. Resultados: Se diagnosticó leishmaniosis visceral en 13,2 por ciento de niños hospitalizados por fiebre prolongada, 90,9 por ciento de procedencia rural y 59,1 por ciento desnutridos. El 77,3 por ciento de los casos recibió antimoniales, 90,9 por ciento tuvo estadía hospitalaria mayor de 21 días y el 36,4 por ciento se complicó con neumonía. Conclusiones: La leishmaniosis visceral es una entidad relativamente frecuente en niños admitidos por fiebre prolongada en el Hospital Italiano, predominan los varones desnutridos, mayores de cinco años de edad, procedentes de zonas rurales. La fiebre y la esplenomegalia son manifestaciones clínicas constantes, la anemia y la leucopenia los principales hallazgos de laboratorio. La aplicación de antimoniales es el tratamiento electivo, con larga estadía hospitalaria y la neumonía es la complicación más frecuente(AU)


Introduction: Visceral leishmaniasis is the most severe clinical form of leishmaniasis that mainly affects children and is potentially fatal. Objective: To explain the clinical-epidemiological characterization of visceral leishmaniasis in the pediatric population and its therapeutic response. Methods: It was conducted a retrospective, longitudinal and descriptive study in the Italian Hospital, Djibouti City in the period from September 2016 to August 2017. The sample group was formed by 166 children under 15 years old that were admitted with a diagnosis of prolonged fever without localization focus and the sample was of 22 children with confirmed diagnosis of visceral leishmaniasis. The information was obtained from the clinical records. Twenty variables were operationalized: sociodemographic, clinical, analytical, therapeutic and evolutive ones. Epidat 3.1 proccessor was used. The results were expressed in absolute values and percentages. Results: Visceral leishmaniasis was diagnosed in 13.2 percent children that were admitted in hospital due to prolonged fever, 90.9 percent of them were from rural areas and 59.1 percent were undernourished. 77,3 percent of the cases had antimonial treatment, 90.9 percent had hospital stay for more than 21 days and the 36.4 percent had complications due to pneumonia. Conclusions: Visceral leishmaniasis is a relatively frequent entity in children admitted in the Italian Hospital due to prolonged fever with a predominance of undernourished males, older that five years and from rural areas. Fever and splenomegaly are constant clinical manifestations, and anemia and leucopenia are the main laboratory findings. The use of antimonials is the election treatment with long hospital stay, and pneumonia is the most frequent complication(AU)


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Hospitalization/statistics & numerical data , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/epidemiology , Epidemiology, Descriptive , Retrospective Studies , Longitudinal Studies , Antimony/therapeutic use
2.
Mem. Inst. Oswaldo Cruz ; 115: e190361, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091244

ABSTRACT

Genes associated with wound healing have been shown to be risk factors for cutaneous leishmaniasis (CL) which is caused by Leishmania braziliensis. In this study, we examined whether the genes previously associated with CL influenced the clinical outcome. Patients were genotyped and retrospectively classified as responders, who were cured with a single course of pentavalent antimony (Sbv), or as refractories, who did not respond to Sbv. Patients characterised as responders showed a stronger response to the leishmanin skin test (LST) when compared to the refractory subjects (p = 0.0003). Furthermore, we observed an association between the FLI1 CC genotype and an increased size of ulcers (p = 0.0170). We suggest that the leishmanin skin test may be a predictive tool for therapeutic outcome and reinforce FLI1 as a potential influencer of susceptibility and lesion size in CL.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Wound Healing/genetics , Leishmaniasis, Cutaneous/genetics , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Skin Tests , Case-Control Studies , Retrospective Studies , Leishmaniasis, Cutaneous/pathology , Leishmaniasis, Cutaneous/drug therapy , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genotype , Middle Aged
3.
Rev. Soc. Bras. Med. Trop ; 51(3): 318-323, Apr.-June 2018. tab, graf
Article in English | LILACS | ID: biblio-957424

ABSTRACT

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.


Subject(s)
Humans , Male , Female , Adult , Aged , Aged, 80 and over , Leishmaniasis, Mucocutaneous/drug therapy , Fluconazole/therapeutic use , Amphotericin B/therapeutic use , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Severity of Illness Index , Treatment Outcome , Middle Aged
4.
An. bras. dermatol ; 92(2): 268-269, Mar.-Apr. 2017. graf
Article in English | LILACS | ID: biblio-838041

ABSTRACT

Abstract: Periungual and paronychia-like skin lesions can mimic various diseases, setting up a diagnostic challenge that invariably requires correlation with complementary tests. We report a case of an ulcerated tumor of the nailfold diagnosed as leishmaniasis. Although paronychia-like cutaneous leishmaniasis is a rare variant, its epidemiological relevance in Brazil should prompt dermatologists to include it as a plausible diagnosis thus leading to correct work up and treatment.


Subject(s)
Humans , Male , Young Adult , Leishmaniasis, Cutaneous/pathology , Brazil , Leishmaniasis, Cutaneous/drug therapy , Meglumine/analogs & derivatives , Meglumine/therapeutic use , Antimony/therapeutic use , Antineoplastic Agents/therapeutic use
5.
Rev. Fed. Argent. Soc. Otorrinolaringol ; 24(2): 58-62, 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-908139

ABSTRACT

La leishmaniasis es una zoonosis parasitaria causada por protozoos. Puede afectar la piel y las mucosas o presentarse como una enfermedad visceral. La variedad mucocutánea conduce a la destrucción parcial o completa de las membranas mucosas de la nariz, las fauces y la faringe. Aproximadamente un 90% de los casos con afectación mucocutánea se producen en Brasil, Bolivia y Perú. En nuestro país afecta en forma endémica a las provincias del norte desde principios del siglo XX. Se relata el caso de un paciente de 53 años con odinodisfagia de aproximadamente 6 meses de evolución, asociado a formaciones granulomatosas medio- faciales, en el que se diagnosticó leishmaniasis cutaneomucosa mediante el rescate de amastigotes en muestras tomadas de lesiones de paladar blando para estudio anatomopatológico con tinción de Giemsa. Se realizó tratamiento con meglumina antimoniato con buena evolución clínica a partir de los quince días de instaurado el mismo.


Leishmaniasis is a parasitic zoonosis caused by protozoa. It can affect skin, mucous membranes or presented as visceral disease. Mucocutaneous variety leads to partial or complete destruction of the mucous membranes of the nose, mouth and pharynx. Approximately, 90% of cases with mucocutaneous involvement occurs in Brazil, Bolivia and Peru. In our country it affects endemic to the northern provinces since the beginning of the century. The case of a 53-year-old patient with odinodisphagia of approximately 6 months of evolution, associated with mid-facial granulomatous formations in which cutaneomucous leishmaniasis was diagnosed by rescue of amastigotes in samples taken from lesions of soft palate for anatomopathological study with Staining of Giemsa. Treatment with meglumina antimonia was carried out with good clinical evolution from the fifteen days of the same establishment.


A leishmaniose é uma zoonose parasitária causada por protozoários. Ele pode afectar a pele e membranas mucosas ou presente como doença visceral. variedade mucocutânea conduz à destruição parcial ou completa das membranas mucosas do nariz, boca e faringe. Aproximadamente 90% dos casos com envolvimento mucocutânea ocorrem no Brasil, Bolívia e Peru. Em nosso país que afeta endêmica para as províncias do norte, desde o início do século XX. O caso de um odinodisfagia 53 anos, aproximadamente, 6 meses evolução associada com formações granulomatosas mediofaciais em que a leishmaniose mucocutânea foi diagnosticada por resgatar amastigotas em amostras tomadas a partir de lesões do palato mole para estudo histopatológico contou Giemsa. O tratamento foi realizado com antimoniato de meglumina com boa evolução clínica a partir de quinze dias introduzidas ele.


Subject(s)
Male , Humans , Middle Aged , Leishmaniasis, Mucocutaneous/diagnosis , Leishmaniasis, Mucocutaneous/drug therapy , Antimony/therapeutic use , Granulomatosis, Orofacial/diagnosis , Granulomatosis, Orofacial/therapy , Meglumine/therapeutic use
6.
Brasília; CONITEC; nov. 2015. tab, ilus.
Monography in Portuguese | LILACS, BRISA | ID: biblio-837418

ABSTRACT

Contexto: No Brasil, a leishmaniose tegumentar é uma das doenças infecciosas que merece maior atenção, especialmente devido a sua alta magnitude e ao risco de ocorrência de deformidades permanentes nos indivíduos acometidos. Ela pode se apresentar nas seguintes formas clínicas: cutânea, disseminada, mucosa ou mucocutânea e difusa. No período de 2009 a 2013 foram registrados, em média, 21.395 casos/ano, distribuídos em todas as Unidades Federativas do Brasil. Algumas pesquisas têm demonstrado sucesso no emprego da pentoxifilina como coadjuvante no tratamento da leishmaniose mucosa, com desfecho de cura em menor tempo quando comparado ao tratamento convencional. Pergunta: Há evidências de que a pentoxifilina é eficaz e segura no tratamento de pacientes com leishmaniose mucosa? Evidências científicas: Após busca em bases de dados da literatura científica, foram encontradas 4 referências sobre o uso da pentoxifilina no tratamento da leishmaniose mucosa (LM): 3 revisões sistemáticas e 1 ensaio clínico randomizado. Uma das revisões se baseou em uma série de casos de 10 pacientes com LM refratária e as outras 2 revisões sistemáticas incluíram o mesmo ensaio clínico randomizado, já selecionado na busca, com 23 pacientes adultos com LM. Tanto a série de casos, quando o ensaio clínico foram realizados na Bahia e incluíram pacientes infectados por L. braziliensis. Em ambos os estudos, a terapia com pentoxifilina associada ao tratamento padrão com antimonial levou a uma taxa de cura maior e mais rápida das lesões do que a terapia com o antimonial isolado. Os membros da CONITEC presentes na reunião do plenário do dia 05/11/2015 - Deliberaram, por unanimidade, por recomendar a ampliação do uso da pentoxifilina 400mg em \r\nassociação ao antimonial para o tratamento da Leishmaniose Tegumentar Mucosa. A Portaria Nº 67, de 19 de novembro de 2015 - Torna pública a decisão de ampliar o uso da pentoxifilina 400 mg em associação ao\r\nantimonial para o tratamento da leishmaniose tegumentar mucosa no âmbito do Sistema Único de Saúde - SUS.


Subject(s)
Humans , Antimony/therapeutic use , Leishmaniasis, Cutaneous/therapy , Pentoxifylline/therapeutic use , Brazil , Cost-Benefit Analysis , Medication Systems , Technology Assessment, Biomedical , Unified Health System
7.
Rio de Janeiro; s.n; 2015. xv,107 p. tab, graf.
Thesis in Portuguese | LILACS | ID: lil-757010

ABSTRACT

Antimoniais pentavalentes são considerados medicamentos de primeira linha no tratamento das diferentes formas de leishmaniose. O perfil de segurança dos medicamentos à base de antimônio (Sb), entretanto, ainda não foi completamente elucidado. O objetivo deste conjunto de estudos que constam desta tese foi fornecer informações adicionais sobre a segurança de um curso de tratamento com o antimoniato de meglumina (AM). O primeiro estudo investigou o acúmulo e eliminação do Sb do sangue e órgãos de ratos machos adultos tratados com uma dose diária de AM, por um período de 21 dias consecutivos. Foi observado que o antimônio é lentamente eliminado. O segundo estudo avaliou o desenvolvimento pós-natal da prole nascida e amamentada por ratas tratadas na gestação e lactação até o desmame com AM. A transferência de Sb através da placenta e via leite materno para a prole foi determinada. Os resultados mostraram, em geral, que o desenvolvimento pós-natal e a fertilidade dos ratos expostos não foram alterados. Os dados também sugerem que o Sb passa facilmente para o leite e está presente nesta matriz biológica em uma forma química que o torna bem absorvido pelos lactentes. Além disso, nós também investigamos se as atividades das enzimas citocromo P450 hepáticas (CYP), que participam do metabolismo de endo- e xenobióticos, foram alteradas pelo tratamento. Os resultados mostraram que um curso de tratamento de 24 dias com AM causou um consistente declínio das atividades de CYP1A no fígado de camundongos SW e DBA-2, e uma diminuição nas atividades de CYP2B9/10 nas fêmeas de SW, mas não em DBA-2 de ambos os sexos...


Pentavalent antimony compounds are considered as first choice drugs to treat different clinical manifestations of leishmaniasis. The safety profile of antimony-based anti-leishmanial drugs, however, has not been entirely elucidated so far. The objective of the set of experimental studies presented in this thesis was to provide additional information on the safety of a course of treatment with meglumine antimoniate (MA). The first study was an investigation of the accumulation and clearance of antimony (Sb) in the blood and organs of adult male rats treated with a 21-day course of MA. It was observed that residual Sb is slowly eliminated from rat’s organs and blood. The second study evaluated the postnatal development of the offspring born to and nursed by rats treated during gestation and lactation until weaning with MA. The transfer of Sb via placenta and mothers’ milk to the offspring was determined as well. Results showed that offspring postnatal development and fertility remained virtually unaltered after treatment with MA. Data suggested that Sb is transferred into breast milk and is present there in a chemical form that makes this metalloid bioavailable to suckling pups. Furthermore, we investigated whether activities of liver cytochrome P450 enzymes that take part in the metabolism of endogenous and exogenous substances were altered after a course of treatment with MA. It was found that a 24-d course of treatment with MA caused a consistent decline in CYP1A activity in the mouse liver. A decrease of CYP2B9/10 activity was noted in SW females but not in SW males and in DBA-2 of either sex...


Subject(s)
Animals , Antimony/therapeutic use , Leishmaniasis/therapy , Metalloids , Meglumine/therapeutic use , /toxicity , Rodentia
8.
Mem. Inst. Oswaldo Cruz ; 109(4): 499-501, 03/07/2014. tab, graf
Article in English | LILACS | ID: lil-716309

ABSTRACT

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Antimony/adverse effects , Antiprotozoal Agents/adverse effects , Herpes Zoster/etiology , /physiology , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Herpes Zoster/virology , Leishmaniasis, Cutaneous/drug therapy , Virus Activation
9.
Rev. patol. trop ; 43(4): 405-411, 2014. tab
Article in Portuguese | LILACS | ID: lil-752782

ABSTRACT

Os antimoniais pentavalentes (Antimoniato de N-metilglumina – Glucantime®) são fármacosde primeira escolha no tratamento da leishmaniose tegumentar americana (LTA). Apresentama cardiotoxicidade como importante efeito adverso e é evidenciada por alterações noeletrocardiograma de repouso (ECG). O alargamento do intervalo QT corrigido (QTc) é a principale potencialmente mais grave delas. O presente estudo teve como objetivo avaliar as alteraçõesno ECG e sua frequência nos pacientes com LTA tratados com Glucantime® no Serviço deDermatologia de nossa instituição. Para isso, um cardiologista avaliou os ECGs de 15 pacientes entre 18 e 59 anos de idade diagnosticados com LTA. Os exames foram realizados imediatamenteantes, no 7º, 14º e 21º dias do tratamento. Desses pacientes, cinco (33 por cento) desenvolveram algumdistúrbio no eletrocardiograma, cuja frequência foi diretamente proporcional ao tempo de uso dofármaco. Bradicardia sinusal nova foi o mais comum (5/15 pacientes), seguida por alargamento dointervalo QTc (2/15 pacientes, os quais também apresentaram bradicardia). Não houve registro decomplicações graves e nenhum paciente desenvolveu sintomatologia cardiovascular. Em apenasum caso foi necessária a interrupção do tratamento. A frequência de alterações no ECG observada écompatível com a relatada por estudos anteriores sobre o tema. Concluímos que a cardiotoxicidadedos antimoniais pentavalentes se manifestou de forma insidiosa, cumulativa, em proporçãocompatível com os relatos da literatura e sem repercussões clínicas.


The pentavalent antimonial compounds (Meglumine Antimoniate – Glucantime®) are thecornerstone for the treatment of American Cutaneous Leishmaniasis (ACL). Cardiotoxicity is theirprincipal adverse effect, which becomes evident as abnormalities in the resting Electrocardiogram(ECG), the prolongation of the corrected QT interval (QTc) being the most important and potentiallyhazardous of them. The purpose of this study was to evaluate the disturbances on ECG and theirfrequency in patients diagnosed with ACL and treated with Glucantime® at our Institution. Fifteenpatients between 18 and 59 years had their ECGs assessed by a senior cardiologist. The tests wereperformed prior to treatment, as well as on its 7th, 14th and 21st day. Five patients (33 percent) developed anabnormality not previously observed, and frequency correlated with the duration of the treatment.The most common was sinus bradycardia (5 of 15 patients), followed by prolongation of the QTcinterval (2 of 15 patients; both also had sinus bradycardia). No major cardiovascular symptomsor complications were reported. Only one patient had to interrupt the treatment. This proportionof ECG disturbances is consistent with previous studies on the subject. We conclude that thecardiotoxicity of the pentavalent antimonial drugs occurred insidiously in a percentage of patientscompatible with the literature, and was not associated with major clinical complications.


Subject(s)
Humans , Antimony/therapeutic use , Electrocardiography , Leishmaniasis, Cutaneous
11.
An. bras. dermatol ; 87(1): 148-149, Jan.-Feb. 2012. ilus
Article in English | LILACS | ID: lil-622468

ABSTRACT

The vast majority of cases of cutaneous leishmaniasis are represented by limb injuries. A female patient, white, presented an ulcer with infiltrated borders located on the fourth finger of the left hand following occupational exposure in an area of native forest. Diagnosis of cutaneous leishmaniasis caused by Leishmania of the subgenus Viannia was confirmed. The patient failed to respond to treatment with antimony, but achieved clinical cure after this was associated with pentoxifylline. The case highlights the rarity of the periungual location of the leishmanial lesion and the difficulties encountered in therapy.


A grande maioria dos casos de leishmaniose tegumentar é representada por lesões nos membros. Paciente feminina, branca, diabética, apresentou úlcera com bordas infiltradas, localizada no quarto quirodáctilo esquerdo, após exposição ocupacional em área de mata nativa. Foi confirmado o diagnóstico de leishmaniose tegumentar por Leishmania do subgênero Viannia. Não respondeu ao tratamento com antimonial, mas obteve cura clínica após associação com a pentoxifilina. O caso destaca-se pela raridade da localização periungueal da lesão leishmaniótica e pela dificuldade terapêutica.


Subject(s)
Adult , Female , Humans , Leishmaniasis, Cutaneous/pathology , Antimony/therapeutic use , Leishmania/classification , Leishmaniasis, Cutaneous/drug therapy , Pentoxifylline/therapeutic use , Treatment Outcome
12.
Rio de Janeiro; s.n; 2012. xvi,93 p. tab, ilus.
Thesis in Portuguese | LILACS | ID: lil-734200

ABSTRACT

Pacientes com leishmaniose cutânea (LC) apresentam variada resposta à terapêutica com antimoniais pentavalentes, desde a cura clínica até a falha terapêutica e reativação da doença. Aspectos relacionados ao hospedeiro, aos parasitos, aos diferentes fármacos e aos diferentes esquemas terapêuticos podem influenciar nesse desfecho. No estado do Rio de Janeiro, tem sido relatada resposta terapêutica favorável a baixas doses de antimoniais (5mg Sbv/kg/dia). É possível que esse resultado esteja relacionado a características genéticas das subpopulações de Leishmania braziliensis que circulam nesse Estado. Neste estudo investigou-se a variabilidade genética e a sensibilidade in vitro ao antimoniato de meglumina de amostras de L. braziliensis, comparando isolados obtidos de pacientes com LC respondedores ou não respondedores ao tratamento com 5mg Sbv/Kg/dia. Foram estudadas amostras de pacientes diagnosticados no Laboratório de Vigilância em Leishmanioses (Vigileish) do Instituto de Pesquisa Clínica Evandro Chagas - Fundação Oswaldo Cruz entre 1999 e 2011. Utilizamos uma amostra de conveniência compreendendo 54 isolados recuperados do banco de cepas do Vigileish, as quais foram distribuídas em quatro subgrupos obedecendo a critérios de inclusão: RRJ) Respondedores ao primeiro curso de tratamento, com infecção adquirida no estado do Rio de Janeiro; NRRJ) Não respondedores ao primeiro curso de tratamento, com infecção no estado do Rio de Janeiro; ROE) Respondedores ao tratamento, com infecção adquirida em outros estados brasileiros e NROE) Não respondedores, com infecção em outros estados brasileiros...


A metodologia utilizada compreendeu inicialmente a caracterização das amostras pela técnica de isoenzimas e após, avaliação da sensibilidade ao antimoniato de meglumina por diluição limitante (DL50) utilizando formas promastigotas e análise da variabilidade genética por Low-Stringency Single-Specific-Primer (LSSP-PCR). Dados clínicos e laboratoriais relacionados ao diagnóstico dos pacientes e aos resultados obtidos neste estudo foram analisados estatisticamente por cálculos em Excel e usando o programa GraphPadPrism 5.0. Os níveis da dose letal de 50 por cento (DL50) das amostras variaram, respectivamente, de 1.9 a 6.0 mg/mL e de 2.3 a 6.4 mg/mL para pacientes respondedores ao tratamento e para pacientes não respondedores, e os valores médios para cada grupo apresentaram diferença significativa (p=0,0007). A diferença se manteve quando os grupos foram analisados separadamente por local de origem. Entretanto, não foi possível associar tal resultado a padrões genéticos dos parasitos estudados após análise dos dendrogramas gerados pela técnica de LSSP-PCR. Os valores médios da Intradermorreação de Montenegro (IDRM) foram significativamente maiores em pacientes respondedores (p= 0,0301). É possível que, no grupo estudado, fatores relacionados ao hospedeiro sejam mais importantes para variação da resposta terapêutica que os fatores genéticos do parasito e que o resultado da IDRM possa ser um indicativo de resposta terapêutica na LC...


Subject(s)
Humans , Antimony/therapeutic use , Leishmania braziliensis , Leishmaniasis, Cutaneous , Intradermal Tests
13.
Rio de Janeiro; s.n; 2011. xii,63 p. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: lil-728002

ABSTRACT

Os antimoniais pentavalentes representam a principal opção para tratamento das leishmanioses, sendo utilizado no Brasil, o antimoniato de meglumina (Glucantime). A variabilidade da resposta ao tratamento pode estar condicionada a fatores relacionados ao hospedeiro, aos parasitas ou mesmo aos esquemas terapêuticos empregados. Neste estudo, avaliamos amostras de Leishmania (Viannia) braziliensis em ensaios in vitro quanto à sensibilidade ao antimoniato de meglumina. Foram comparadas as DL50 observadas, tanto para formas promastigotas quanto para formas amastigotas, de amostras isoladas no momento do diagnóstico antes do tratamento (amostra A) e de amostras isoladas após o primeiro ciclo de tratamento (amostra B). Sete pares de amostras (A e B) foram selecionados, sendo quatro isolados de pacientes com falha terapêutica e três de pacientes com reativação. As formas promastigotas foram expostas a concentrações de antimoniato de meglumina entre 3,955 mig e 8,1 mg/mL e avaliadas após 24 e 48 horas de exposição. As formas amastigotas, em macrófagos murinos, foram expostas a concentrações de 20, 40 e 80 mig/mL de antimoniato de meglumina, cuja cinética de infecção foi avaliada em intervalos de 0, 24, 48 e 72 horas, baseada em dois parâmetros: percentual de células infectadas e número médio de amastigotas por macrófago. Todas as amostras B de formas promastigotas apresentaram valores da DL50 superiores aos obtidos com as amostras A, exceto para as amostras de um paciente. Nos ensaios com formas amastigotas, as amostras B apresentaram valores da DL50 mais elevados que a amostra A em 4 casos, com aumentos que variaram de 17 a 20 porcento em 3 pacientes e de 100 porcento em um caso. Nos demais pacientes, os valores da DL50 de A e B foram semelhantes. Dos sete pacientes estudados, um abandonou o tratamento e seis apresentaram cura, após retratamento, pelo uso da Anfotericina B (4 casos) ou antimoniato de meglumina (2 casos). Não foi possível correlacionar os resultados obtidos neste estudo com a clínica ou a resposta ao tratamento. É possível que outros fatores relacionados aos pacientes, tais como a condição imunológica e a resposta frente à infecção possam influenciar na resposta à terapêutica antimonial.


Pentavalent antimonials are the first drug of choice for leishmaniasis treatment and in Brazil meglumine antimoniate (Glucantime) is used. The variability of the response to treatment may be conditioned to factors related to the host, the parasites or even the therapeutic plan. In this study we assessed the susceptibility to meglumine antimoniate of samples of Leishmania (Viannia) braziliensis in in vitro tests. We compared the DL50 of both promastigote and amastigote forms of samples isolated at diagnosis before treatment (sample A) and samples isolated after the first cycle of treatment (sample B). Seven pairs of samples (A and B) were selected, four isolated from patients with treatment failure and three from patients with reactivation. The promastigote forms were exposed to meglumine antimoniate concentrations between 3,955 mig and 8,1 mg/mL and were assessed after 24 and 48 hours of exposition. The amastigotes, in murine macrophages, were exposed to concentrations of 20, 40 and 80 mig/mL of meglumine antimoniate, and the infection kinetics was assessed at time intervals of 0, 24, 48 and 72 hours, through two parameters: percentage of infected cells and average number of amastigotes per macrophage. All B samples of promastigotes presented DL50 values higher than those obtained with A samples, except for one patient. In tests with amastigotes, the B samples showed higher DL50 values than sample A in 4 cases, with increases ranging from 17 to 20 percent in 3 patients and 100 percent increase in one case. In other patients, DL50 values of A and B were similar. One of the seven patients studied abandoned treatment and six were clinically healed after retreatment with Anphotericin B (4 cases) or meglumine antimoniate (2 cases). It was not possible to correlate the results of this study with the clinics or response to treatment. It is possible that other patient related factors such as immunological condition or response to infection may influence the response to antimonial treatment.


Subject(s)
Humans , Antimony/therapeutic use , Leishmania braziliensis , Leishmaniasis, Cutaneous
14.
An. bras. dermatol ; 84(2): 125-128, mar.-abr. 2009. tab
Article in English, Portuguese | LILACS | ID: lil-515914

ABSTRACT

FUNDAMENTOS: O tratamento de primeira escolha da leishmaniose tegumentar americana é a N-metil-glucamina que tem alta toxicidade, exige administração parenteral e nem sempre cura. A azitromicina mostrou ação in vitro e resultado contraditório na doença humana. OBJETIVO: Verificar se a associação N-metil-glucamina+azitromicina é mais eficaz do que N-metil-glucamina no tratamento da leishmaniose experimental. MÉTODOS: 25 camundongos inoculados com a cepa C57BL/6 de L. (L.) amazonensis foram divididos em dois grupos. Um foi tratado com 400mgSbV/kg/dia de N-metil-glucamina associado a 200mg/kg/dia de azitromicina durante 20 dias, e o outro com N-metil-glucamina, na mesma dose, durante o mesmo tempo. Foi feita avaliação clínica e parasitológica com análise estatística. RESULTADO: Na avaliação clínica, pesquisa de amastigotas e das culturas, não houve diferença estatística. Verificou-se, entretanto, diferença significante no resultado das culturas realizadas através de diluição limitante, que desfavoreceu a associação NMG+ azitromicina. CONCLUSÃO: A associação N-metil-glucamina e azitromicina não demonstrou mais eficácia do que o N-metil-glucamina em uso isolado.


BACKGROUND: The first choice treatment for cutaneous Leishmaniasis is N-methyl glucamine: it has high toxicity, requires parenteral administration and cure is not always reached. Azythromycin showed in vitro action and controversial results in humans with the disease. OBJECTIVE: To verify if the association of N-methyl-glucamine - azythromycin is more effective than N-methyl-glucamine alone for the treatment of experimental Leishmaniasis. METHODS: Twenty-five C57BL/6 mice were inoculated with L. (L.) amazonensis strain and divided into two groups. One group was treated with 400mgSbV/kg/day of N-methyl glucamine and 200mg/kg/day of azythromycin for 20 days and the other group received the same dose of N-methyl glucamine alone during the same period of time. Clinical and parasitological evaluations were submitted to statistical analyses. RESULTS: There was no statistical difference in clinical analysis, in amastigotes investigation and in cultures. There were significant differences in cultures using limiting dilution, which showed lower efficacy of the association N-methyl glucamine -azythromycin. CONCLUSION: N-methyl glucamine-azythromycin association was not more effective than N-methyl glucamine alone.


Subject(s)
Animals , Male , Mice , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Azithromycin/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Meglumine/analogs & derivatives , Antimony/administration & dosage , Azithromycin/administration & dosage , Disease Models, Animal , Drug Administration Schedule , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Meglumine/administration & dosage , Meglumine/therapeutic use , Random Allocation
15.
Rev. ciênc. farm. básica apl ; 29(3): 223-230, 2008.
Article in Portuguese | LILACS | ID: lil-530185

ABSTRACT

A leishmaniose é uma parasitose causada porprotozoários do gênero Leishmania. É uma doença endêmica que abrange mais de 80 países, incluindo alguns do continente europeu e, principalmente, países sub-desenvolvidos ou em desenvolvimento. Nesta revisão discorre-se sobre as opções terapêuticas tradicionais e atuais, cuja atividade leishmanicida pode conduzirao desenvolvimento racional de novos fármacos. Ressaltando-se o uso de produtos naturais na pesquisa e tratamento de Leishmaniose (ex. quinolonas, chalconase extratos brutos).


Subject(s)
Leishmaniasis/therapy , Plants, Medicinal , Antimony/therapeutic use , Chalcones , Plant Extracts , Quinolones
16.
Mem. Inst. Oswaldo Cruz ; 102(5): 625-630, Aug. 2007. graf
Article in English | LILACS | ID: lil-458636

ABSTRACT

Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4+ as compared to CD8+ Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-gamma) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-gamma) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-gamma), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.


Subject(s)
Animals , Female , Humans , Male , Antigens, Protozoan/immunology , Leishmania braziliensis/immunology , Leishmaniasis, Cutaneous/immunology , Lymphocyte Activation/immunology , T-Lymphocytes/immunology , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , /immunology , /immunology , Cells, Cultured , Cytokines/immunology , Endemic Diseases , Leishmaniasis, Cutaneous/drug therapy , Organometallic Compounds/therapeutic use
17.
Rev. Inst. Med. Trop. Säo Paulo ; 49(4): 235-238, Jul.-Aug. 2007. tab
Article in English | LILACS | ID: lil-460231

ABSTRACT

An open trial to evaluate the azithromycin efficacy in cutaneous leishmaniasis patients was carried out in Manaus (AM), where Leishmania (Viannia) guyanensis is the main etiologic agent. Forty-one patients with skin lesions of less than 12 weeks duration, without specific treatment for the last three months and a positive imprint to Leishmania sp. were included. From these, 31 (75.6 percent) were male with median age of 30.2. All of them received a daily-single oral dose of 500 mg of azithromycin for ten days. At 25th day, 16 (39 percent) presented therapeutic failure and received intramuscular pentavalent antimonial, four were considered lost, 21, that had improved or were inaltered received another ten-day series of azithromycin and were monthly followed, but nine (21.9 percent) of them presented a poor clinical response and switched to intramuscular pentavalent antimonial on day 55. Of the 12 remaining cases evaluated on day 55, despite of clinical improvement, three asked for antimony therapy and 9 (21.9 percent) continued the follow-up but, only three were cured on 55th, 85th and 115th days, and six did not come back for final evaluation. The intention-treatment overall response rate was 22 percent and whole cure was seen in three (7.3 percent) of cases. Thus, azithromycin showed a low efficacy to treat cutaneous leishmaniasis in Manaus.


Para avaliar a eficácia da azitromicina na leishmaniose cutânea, foi realizado ensaio clínico em Manaus, Amazonas, onde o agente etiológico predominante é a Leishmania (Viannia) guyanensis. Incluídos 41 pacientes com lesões de menos de 12 semanas, sem história de tratamento específico nos últimos três meses e com esfregaço positivo para Leishmania sp. Destes, 31 (75,6 por cento) eram masculinos, idade média 30,2 anos. Todos receberam azitromicina 500 mg em dose única oral, diária, por 10 dias. No dia 25°, 16 (39 por cento) pioraram e receberam antimonial pentavalente via intramuscular por 20 dias e, 21 (61 por cento) que apresentaram melhora da lesão ou esta permanecia inalterada no 25° dia, receberam outro ciclo de 10 dias de azitromicina e foram acompanhados mensalmente. Destes, nove (21,9 por cento) apresentaram piora das lesões na avaliação do dia 55 e iniciaram tratamento com antimonial neste dia. Dos 12 que permaneceram no estudo, porque tinham melhorado clinicamente, três optaram por tratamento com antimonial pentavalente no 55° dia e três apresentaram reepitelização completa das lesões nos dias 55°, 65° e 115°. Seis pacientes não retornaram para avaliação final. Análise por tentativa de tratamento foi 22 por cento e cura confirmada em três (7,3 por cento) casos. Estes resultados mostraram que azitromicina tem baixa eficácia para tratar leishmaniose em área onde a Leishmania (Viannia) guyanensis é o agente etiológico predominante.


Subject(s)
Humans , Animals , Male , Female , Adolescent , Adult , Middle Aged , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Antimony/therapeutic use , Leishmania guyanensis , Treatment Outcome
18.
Article in English | IMSEAR | ID: sea-16638

ABSTRACT

Indian visceral leishmaniasis (VL) is a parasitic disease caused by a haemoflagellete Leishmania donovani and transmitted by the bite of sand fly Phlebotomus argentipes. It affects various age groups. In India about 1,00,000 cases of VL are estimated to occur annually; of these, the State of Bihar accounts for over than 90 per cent of the cases. Diagnosis of VL typically relies on microscopic examination of tissue smears but serology and molecular methods are better alternatives currently. Notwithstanding the growing incidence of resistance, pentavalent antimony complex has been the mainstay for the treatment of VL during the last several decades. The second line drugs such as amphotericin B, lipid formulations of amphotericin B, paromomycin and recently developed miltefosine are the other alternatives. In spite of significant development in various areas of Leishmania research, there is a pressing need for the technological advancement in the understanding of immune response, drug resistance and the pathogenesis of leishmaniasis that could be translated into field applicable and affordable methods for diagnosis, treatment, and control of the disease.


Subject(s)
Aminoquinolines/chemistry , Amphotericin B/pharmacology , Animals , Antimony/therapeutic use , Antiprotozoal Agents/pharmacology , Drug Resistance , Enzyme-Linked Immunosorbent Assay , Humans , India , Leishmania/metabolism , Leishmaniasis, Visceral/diagnosis , Lipids/chemistry , Paromomycin/chemistry , Public Health/methods , Sensitivity and Specificity
19.
J Postgrad Med ; 2003 Jan-Mar; 49(1): 39-49
Article in English | IMSEAR | ID: sea-116417

ABSTRACT

Herein we review the particular aspects of leishmaniasis associated with HIV infection. The data in this review are mainly from papers identified from PubMed searches and from papers in reference lists of reviewed articles and from the authors' personal archives. Epidemiological data of HIV/Leishmania co-infection is discussed, with special focus on the influence of Highly Active Antiretroviral Therapy (HAART) on incidence of leishmaniasis and transmission modalities. Microbiological characteristics, pathogenesis, clinical presentation and specific treatment of the co-infection are also presented.


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Animals , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV/pathogenicity , HIV Infections/complications , Humans , Leishmania/pathogenicity , Leishmaniasis/complications , Risk Factors
20.
Rev. Soc. Bras. Med. Trop ; 35(6): 629-633, nov.-dez. 2002. tab
Article in English | LILACS | ID: lil-340063

ABSTRACT

Although treatment of visceral leishmaniasis with pentavalent antimony is usually successful, some patients require second-line drug therapy, most commonly with amphotericin B. To identify the clinical characteristics that predict an inadequate response to pentavalent antimony, a case-control study was undertaken in Teresina, Piaui, Brazil. Over a two-year period, there were 19 cases of VL in which the staff physicians of a hospital prescribed second-line therapy with amphotericin B after determining that treatment with pentavalent antimony had failed. The control group consisted of 97 patients that were successfully treated with pentavalent antimony. A chart review using univariate and multivariate analysis was performed. The cure rate was 90 percent with amphotericin B. The odds ratio for the prescription of amphotericin B was 10.2 for children less than one year old, compared with individuals aged over 10 years. Patients who presented coinfection had an OR of 7.1 while those on antibiotics had an OR of 2.8. These data support either undertaking a longer course of therapy with pentavalent antimony for children or using amphotericin B as a first-line agent for children and individuals with coinfections. It also suggests that chemoprophylaxis directed toward bacterial coinfection in small children with VL may be indicated


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Amphotericin B/therapeutic use , Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Leishmaniasis, Visceral/drug therapy , Antimony/adverse effects , Case-Control Studies , Treatment Failure
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