Body weight as a determinant of clinical evolution in hamsters (Mesocricetus auratus) infected with Leishmania (Viannia) panamensis.

The clinical outcome of infection with Leishmania species of the subgenus Viannia in hamster model (Mesocricetus auratus) has shown to be different depending on experimental protocol. Body weight has been a relevant determinant of the clinical outcome of the infection in hamsters with visceral leishmaniasis but its importance as a clinical parameter in hamsters with cutaneous leishmaniasis is not known. In this study, the clinical evolution of infection with L. (V) panamensis was evaluated in juvenile and adult male hamsters during 11 weeks by comparing clinical parameters such as attitude, temperature, respiratory rate, appearance of the stool, and body weight between infected and non-infected groups. Results showed that body weight decreased in adult hamsters after infection by L. (V) panamensis; this observation supports the use of body weight as an additional parameter to define the management or treatment of cutaneous leishmaniasis in infected adult hamsters used as an animal experimental model for leishmaniasis.

BODY WEIGHT AS A DETERMINANT OF CLINICAL EVOLUTION IN HAMSTERS (Mesocricetus auratus) INFECTED WITH Leishmania (Viannia) panamensis / Peso como determinante da evolução clínica em hamsters (Mesocricetus auratus) infectados com Leishmania (Viannia) panamensis

SUMMARY The clinical outcome of infection with Leishmania species of the subgenus Viannia in hamster model (Mesocricetus auratus) has shown to be different depending on experimental protocol. Body weight has been a relevant determinant of the clinical outcome of the infection in hamsters with visceral leishmaniasis but its importance as a clinical parameter in hamsters with cutaneous leishmaniasis is not known. In this study, the clinical evolution of infection with L. (V) panamensis was evaluated in juvenile and adult male hamsters during 11 weeks by comparing clinical parameters such as attitude, temperature, respiratory rate, appearance of the stool, and body weight between infected and non-infected groups. Results showed that body weight decreased in adult hamsters after infection by L. (V) panamensis; this observation supports the use of body weight as an additional parameter to define the management or treatment of cutaneous leishmaniasis in infected adult hamsters used as an animal experimental model for leishmaniasis. .

RESUMO O resultado clínico da infecção por espécies de Leishmania do subgênero Viannia no modelo de hamster (Mesocricetus auratus) tem se mostrado diferente, dependendo do protocolo experimental. O peso corporal tem sido um importante determinante da evolução clínica da infecção em hamsters com leishmaniose visceral, mas sua importância como parâmetro clínico em hamsters com leishmaniose cutânea não é conhecido. Neste estudo, a evolução clínica da infecção com L. (V) panamensis foi avaliada em jovens e adultos hamsters machos durante 11 semanas, comparando os parâmetros clínicos tais como a atitude, a temperatura, a frequência respiratória, a aparência das fezes, e o peso corporal entre infectado e grupos não infectados. Os resultados mostraram que o peso corporal diminuiu em hamsters adultos após infecção por L. (V) panamensis. Esta observação suporta a utilização do peso corporal, como um parâmetro adicional para definir a administração ou o tratamento de leishmaniose cutânea em hamsters adultos infectados usados como modelo animal experimental para a leishmaniose. .

Detección de Leishmania braziliensis en lesión mucosa con 16 años de evolución: Registro de un caso / Detection of Leishmania braziliensis in a mucosal lesion with 16 years of evolution: A case report

Se registra, en un paciente masculino de 48 años, la detección de Leishmania (Viannia) braziliensis en muestra de lesión mucosa crónica con 16 años de evolución clínica. El caso presentado cursa con perforación del tabique nasal no evidenciándose lesión cutánea primaria sugestiva de leishmaniasis. Por su ocupación el paciente ha frecuentado, por largos períodos, bosques en áreas endémicas para leishmaniasis en el occidente de Venezuela. Continuas evaluaciones clínicas, inmunológicas e histopatológicas realizadas durante varios años fallaron en establecer un diagnóstico certero incrementando la severidad del caso. Exámenes recientes realizados en nuestro laboratorio revelan la presencia de amastigotes en muestras de la lesión nasal activa en extendidos coloreados con tinción de Giemsa. La identificación del parásito como L. braziliensis y la verificación de la infección por este parásito en el paciente, fue lograda por ensayos de PCR y Western Blot, respectivamente. Se concluye que el caso presentado sufre una leishmaniasis mucocutánea de vieja data con una baja respuesta inmunológica, a juzgar por la frecuente negatividad en pruebas de IDR y/o la detección de anticuerpos circulantes anti-Leishmania. Se discute sobre la imprecisión diagnóstica en el caso presentado y se advierte sobre el riesgo epidemiológico potencial de casos similares.

The detection of Leishmania (Viannia) braziliensis from a chronic mucosal lesion with 16 years of clinical evolution in a 48 years old male patient is reported. The patient showed destruction of the nasal septal cartilage with no evidence of primary leishmanial lesion. Due to his professional work he frequently visited areas of western Venezuela where leishmaniasis is endemic. Frequent clinical, immunologic and histopathologic evaluations carried out during several years failed to establish a right diagnosis, increasing the severity of the mucosal lesion. The finding of a sparse number of amastigotes in a sample from the mucosal lesion stained by Giemsa stain, suggested a mucosal infection by Leishmania. The identification of the parasite as L. braziliensis and the verification of the infection by this parasite in the reported case were carried out using a PCR assay and a Western Blot test, respectively. It is concluded that the patient was suffering a long-lasting, reluctant to heal and severe lesion with a low immunological response due to infection by L. braziliensis causing mucocutaneous leishmaniasis (MCL). The fail in the diagnosis of this particular case of MCL and the potential epidemiological risk in similar cases are discussed.

First case of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in Suriname.

The main causative agent of cutaneous leishmaniasis (CL) in Suriname is Leishmania (Viannia) guyanensis. This case report presents a patient infected with Leishmania (Viannia) braziliensis, a species never reported before in Suriname. This finding has clinical implications, because L. braziliensis has a distinct clinical phenotype characterized by mucocutaneous leishmaniasis, a more extensive and destructive form of CL that requires different treatment. Clinicians should be aware that chronic cutaneous ulcers in patients from the Guyana region could be caused by L. braziliensis.

Geographic clustering of leishmaniasis in northeastern Brazil.

To determine whether disease outcomes and clades of Leishmania braziliensis genotypes are associated, we studied geographic clustering of clades and most severe disease outcomes for leishmaniasis during 1999-2003 in Corte de Pedra in northeastern Brazil. Highly significant differences were observed in distribution of mucosal leishmaniasis versus disseminated leishmaniasis (DL) (p<0.0001). Concordance was observed between distribution of these disease forms and clades of L. braziliensis genotypes shown to be associated with these disease forms. We also detected spread of DL over this region and an inverse correlation between frequency of recent DL diagnoses and distance to a previous DL case. These findings indicate that leishmaniasis outcomes are distributed differently within transmission foci and show that DL is rapidly spreading in northeastern Brazil.

New world cutaneous leishmaniasis in travellers.

As travel to Latin America has become increasingly common, cutaneous leishmaniasis is increasingly seen among returning travellers--eg, the number of observed cases has doubled in the Netherlands and tripled in the UK in the past decade. A surprisingly high proportion of cases were acquired in rural or jungle areas of the Amazon basin in Bolivia. The clinical manifestations range from ulcerative skin lesions (cutaneous leishmaniasis) to a destructive mucosal inflammation (mucocutaneous leishmaniasis), the latter usually being a complication of infection with Leishmania (Viannia) braziliensis. PCR is now the diagnostic method of choice, since it has a high sensitivity and gives a species-specific diagnosis, allowing species-specific treatment. Treatment of cutaneous leishmaniasis aims to prevent mucosal invasion, to accelerate the healing of the skin lesion(s), and to avoid disfiguring scars. Pentavalent antimonials drugs are still the drug of choice for many patients. However, a high rate of adverse events, length of treatment, and relapses in up to 25% of cases highlight the limitations of these drugs. Although only used in a small number of patients thus far, liposomal amphotericin B shows promising results. Further studies are needed to find efficacious and better-tolerated drugs for new world leishmaniasis.

Up-regulation of Th1-type responses in mucosal leishmaniasis patients.

The cytokine profile produced by peripheral blood mononuclear cells (PBMC) in response to leishmania antigens and the ability of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) to modulate the immune response were evaluated in 21 mucosal leishmaniasis patients. Patients with mucosal disease exhibited increased gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) secretion and decreased IL-10 secretion compared to patients with classical cutaneous leishmaniasis. CD4(+) Th1 cells were the main source of IFN-gamma and TNF-alpha production in mucosal leishmaniasis patients. Evaluation of cytokine gene expression in PBMC of these patients showed that there was strong up-regulation of IFN-gamma transcripts upon stimulation with leishmania antigen, in contrast to the baseline levels of IL-10 mRNA. IL-10 suppressed IFN-gamma production by 48% in cell cultures from cutaneous leishmaniasis patients and by 86% in cell cultures from healthy subjects stimulated with purified protein derivative, whereas in similar conditions IL-10 suppressed IFN-gamma production by 19% in cell cultures from mucosal leishmaniasis patients stimulated with leishmania antigen. TGF-beta suppressed IFN-gamma levels to a greater extent in healthy subjects than in mucosal leishmaniasis and cutaneous leishmaniasis patients. These data indicate that a poorly modulated T-cell response in mucosal leishmaniasis patients leads to production of high levels of proinflammatory cytokines, such as IFN-gamma and TNF-alpha, as well as a decreased ability of IL-10 and TGF-beta to modulate this response. These abnormalities may be the basis for the pathological findings observed in this disease.

Intermediate or chronic cutaneous leishmaniasis: leukocyte immunophenotypes and cytokine characterisation of the lesion.

The American cutaneous forms of leishmaniasis include immune-responder individuals with localised cutaneous leishmaniasis (LCL) and non-responder individuals with diffuse cutaneous leishmaniasis (DCL). Patients with intermediate or chronic cutaneous leishmaniasis (ICL) have increased morbidity due to the length of their illness, atypical forms and areas of compromise. In the present study, we evaluated the expression of the leukocyte antigens (CD4, CD8, CLA: cutaneous lymphocyte antigen, CD69, CD83 and CD1a) and cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta 1) in the lesions of patients with ICL (n = 18) using an immunocytochemical procedure. ICL results were compared with the information for LCL (n = 19) and DCL (n = 4). The numbers of CD4+ and CD8+ T cells in ICL were similar to those of LCL lesions, but significantly different (P < or = 0.05) from DCL lesions. LCL lesions have about half the numbers of early activated CD69+ cells as ICL, but most are CLA+ skin homing memory T cells, whereas ICL lesions have the highest number of CD69+ T cells, but about one-third of these cells expressed CLA. This suggests that the granuloma of ICL patients contains many activated T cells that are unprimed to cutaneous-launched antigens, thus contributing to an aberrant immune response. In contrast, DCL granulomas presented the lowest numbers of activated CD69+ and CLA+ cells, associated with the characteristic tolerogenic state of these patients. The immunolocalisation of cytokines showed a mixed cytokine pattern in ICL lesions with many positive cells for IL-10, TGF-beta 1, IL-4 and IFN-gamma, with a preponderance of the first two, and different from the prevalent Th1 and Th2 responses associated with LCL and DCL lesions, respectively. CD1a+ Langerhans cells were decreased (P < or = 0.05) in both ICL (271 +/- 15 cells/mm2) and DCL (245 +/- 19 cells/mm2) as compared to LCL (527 +/- 54 cells/mm2) epidermis. The percentage of IL-10+ epidermal Langerhans cells in ICL (33.69), from the total CD1a+ population, was higher than in LCL (17.45). In addition, fewer CD83+ primed Langerhans cells were present in ICL epidermis. The diminished participation of epidermal Langerhans cells, causing a defective signalling by the epidermis, in ICL lesions may account for the tissue-damaging state observed in these patients.

Leishmaniose tegumental americana com extenso acometimento de mucosas: relato de caso e revisäo da literatura / American diffuse leishmaniosis with extensive attacking of mucous membranes: case report and literature review

A leishmaniose tegumentar americana é uma doença de evolução crônica que acomete, isoladamente ou em associação, a pele e as mucosas do nariz, boca, faringe e laringe (4). É causada por protozoários do gênero Leishmania e transmitida por insetos do gênero flebotomíneos. Os autores fazem uma revisão bibliográfica e relatam um caso de leishmaniose mucocutânea em um paciente de 26 anos, que apresentava lesão no palato duro e toda orofaringe, evoluindo com emagrecimento importante. A lesão foi diagnosticada através de biópsia de mucosa, a qual evidenciou o protozoário. O interesse do relato se dá pela ascensão do número de casos de leishmaniose em nosso meio, sendo importante o diagnóstico diferencial

Leishmaniose tegumentar americana (LTA) difusa em paciente infectado pelo vírus da imunodeficiência humana (HIV): relato de caso / American cutaneous leishmaniasis (LTA) in an hiv-positive patient: a case report

Paciente acompanhado pelo Setor de Doenças Infecciosas e Parasitárias do Hospital Universitário Regional do Norte do Paraná (HURNP), desde janeiro de 1991, com o diagnóstico de infecçäo pelo vírus da imunodeficiência humana (HIV), feito na ocasiäo por teste imunoenzimático (Elisa) e Western Blot. Manteve-se assintomático até 1994, quando passou a apresentar lesäo papuloeritematosa ulcerada no punho direito, cuja biópsia permitiu estabelecer o diagnóstico de leishmaniose tegumentar americana. Foi, entäo, submetido a tratamento com N-metilglucamina, sem resposta clínica. A terapêutica com anfotericina B, iniciada em seguida, teve bom resultado, mas foi interrompida pelo paciente, que näo mais compareceu ao ambulatório. Em março de 1995, retornou ao Serviço, com quadro de monilíase oral, diarréia e lesöes maculares, melanodérmicas e polimórficas generalizadas, predominantemente localizadas nos membros superiores e inferiores. A biópsia dessas lesöes confirmou, mais uma vez, o diagnóstico de LTA, tendo sido positiva (1:640) a pesquisa no soro, por imunofluorescência indireta, de IgG anti-Leishmania braziliensis. Foi, entäo reintroduzido o tratamento com anfotericina B

Manegement of opportunistic infections in HIV + patients: contrasts between Europe and South America

The author discuses the management of some opportunistic diseases more commonly observed in South American AIDS patients than in European ones. Characteristics of coinfection with HIV and leprosy, paracoccidioidomycosis, Chagas's disease, mucocutaneous leishmaniasis, malaria, disseminated BCG and strongyloidiasis are reviewed, with special emphasis on preferred therapeutic schedules for these conditions.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose / The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis

Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

[The evaluation of the tolerance and nephrotoxicity of pentavalent antimony administered in a dose of 40 mg Sb V/kg/day, 12/12 hr, for 30 days in the mucocutaneous form of leishmaniasis]. / Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40 mg Sb V/kg/dia, de 12/12 h, por 30 dias na forma cutâneo-mucosa de leishmaniose.

The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40 mg/kg/day of pentavalent antimony (Sb V), in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxic effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40 mg Sb/kg/day was less tolerated on account of its renal toxic effects. This scheme seems not be superior than the currently preconized scheme of 20 mg of Sb V/kg/day during 30 days.

Leishmania braziliensis spp. in the nasal mucosa of guinea pigs inoculated in the tarsi.

Two lots of 20 young male guinea pigs were inoculated subcutaneously in the tarsi with 10(4) amastigotes of Leishmania braziliensis braziliensis or L. b. guyanensis to study the susceptibility of this Neotropical hystricomorph rodent the autochthonous parasites. Almost 50% of the animals showed lesions in the inoculation site and had parasitizations that were infective to hamsters, as shown by inoculating homogenates of the dermal lesion, of the spleen, of the liver, and of the nasal mucosa into hamsters at 20, 40, 60, and 120 days after inoculation of the guinea pig. Smears of the above organs showed the presence of amastigotes. Parasites inoculated into the tarsi were detected early in the skin, spleen, and liver of the guinea pig host. Blood cultures made by cardiopuncture on sacrifice of the guinea pigs were uniformly negative. The nasal mucosa of nearly all animals positive in the skin or viscera was invaded early by the parasites, although with greater frequency between 60 and 120 days post-inoculation. The use of this model for the study of mucocutaneous parasitism by L. braziliensis is discussed, together with the phenomena of parasitism at a distance from the inoculation site, the temperature of the body regions affected, and the possible genetic influence on susceptibility of the guinea pig to L. braziliensis.

Electrocardiographic alterations during treatment of mucocutaneous leishmaniasis with meglumine antimoniate and allopurinol.

The electrocardiographic (ECG) changes in Bolivian patients with mucocutaneous leishmaniasis, treated with meglumine antimoniate and allopurinol, were evaluated. Electric changes due to the antimonial compound appeared in 45% of the patients, and consisted of repolarization alteration, principally affecting the T wave and the S-T segment. The changes disappeared within 2 months following the end of the antimonial treatment. In patients with associated Chagas disease and leishmaniasis, antimonial therapy did not aggravate the ECG changes characteristic of Chagasic cardiopathy.

Leishmaniasis muco-cutánea (Espundia) en México. Informe de 3 casos en el estado de Tabasco / Mucocutaneous leishmaniasis (espundia) in Mexico. A report of 3 cases from the state of Tabasco

Hay indicios en la literatura médica nacional, sugestivos de la existencia de casos de leishmaniasis muco-cutánea (Espundia). Nosotros, estudiamos las formas cutáneas localizada y diseminada, hemos tambien reconocido 3 casos de la variante muco-cutánea, con las suficientes bases de metodología diagnóstica, que de manera inequívocada sustentan a esta entidad, como una forma patológica primaria en nuestro país. Se discute la literatura mexicana, lo mismo que nuestras observaciones .

Funçäo renal em pacientes com leishmaniose muco-cutânea tratados com antimoniais pentavalentes / Renal function in patients with mucocutaneous leishmaniasis treated with pentavalent antimonials

Avaliou-se a funçäo renal em 10 pacientes com leishmaniose muco-cutânea tratados com glucantime (antimoniato de Meglumine, Rhodia) ou Pentostam (estibogluconato de sólio, Wellcome). Durante o uso das drogas, verificou-se a existência de um defeito na capacidade concentrante do rim, obtendo-se menores valores da osmolaridade urinária máxima e de depuraçäo negativa máxima de água livre, neste período, em relaçäo aos testes efetuados antes do tratamento. A capacidade de concentraçäo urinária normalizou-se em 5, de 8 pacientes estudados no período de 15 a 30 dias, após a suspensäo dos medicamentos, embora com valores de osmolaridade urinária máxima inferiores aos obtidos antes do tratamento. Em dois pacientes surgiu proteinúria, acima de 150 mg/dia, com o uso dos antimoniais, normalizando-se posteriormente. A depuraçäo de creatinina endógena näo se alterou significativamente com o uso das drogas. Os resultados sugerem que os antimoniais pentavalentes podem levar a uma disfunsäo tubular renal, caracterizada por um defeito na capacidade de concentrar a urina, reversível após a retirada dos medicamentos