Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical f... more Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity.
The technique of polymerase chain reaction (PCR) associated to hybridization was used to screen 1... more The technique of polymerase chain reaction (PCR) associated to hybridization was used to screen 123 samples collected from wild and synanthropic rodents captured in a cutaneous and visceral leishmaniasis endemic area in the State of Minas Gerais, Brazil. The detection of Leishmania spp in naturally infected rodents is of fundamental importance for incriminating them as possible reservoir hosts of the diseases in Minas Gerais. A total of 62 specimens belonging to wild (Thrichomys apereoides, Oryzomys subflavus, Galea spixii, Bolomys lasiurus and Wiedomys pyrrhorhinos) and synanthropic (R. rattus) rodent species were captured in different ecotopes. Blood and skin samples were submitted for PCR analyses followed by molecular hybridization with specific probes for the three Leishmania-species complexes. Fifteen samples were found positive after PCRhybridization and identified as follows: nine belonging to the L. mexicana complex, three to the L. braziliensis complex and three to the L. donovani complex. Positive PCR results were found in 11 out of the 61 (18%) blood samples and in four out of the 62 (6.4%) skin fragments screened. R. rattus and T. apereoides were the most abundant species in the area also presenting high prevalence of natural infection. The presence of parasite DNA belonging to L. braziliensis, L. mexicana and L. donovani complexes was confirmed in several individuals of a rodent species, R. rattus. This work is the first report of the detection of L.
Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease... more Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease forms a spectrum in which the immunologic response of the patient correlates with the clinical and histopathologic classification (1-3). At one end of the spectrum, patients with tuberculoid leprosy have one or several skin lesions in which bacilli can rarely be identified . CD4+ T lymphocytes predominate in these lesions (4-7) and respond to Mycobacterium leßrae in vitro (8). At the other end of the spectrum, patients with lepromatous leprosy have diffuse infiltration of skin and nerves with bacilli-laden macrophages. CD8+ cells predominate in lepromatous lesions and function as antigen-specific Ts cells in vitro (9, 10). The CD4+ lymphocytes derived from these lesions are unresponsive to M. leßrae . Imposed upon this spectrum are the so-called "reactional states" of reversal reaction and erythema nodosum leprosum (ENL)' that are of immunologic interest in understanding mechanisms of immunoregulation in man.
Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been... more Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been reported so far. Four cases are reported here. Parasite diagnosis was performed by classical methods of touch preparations, histopathologic sections, and cultures. In addition, the detection of parasite DNA by the polymerase chain reaction (PCR) was performed in all cases. Parasites were detected by at least one of the classical methods in all primary lesions; however, only the PCR was positive in the recidivant lesions. LRC cases most likely represent a reactivation of an initial infection, probably due to the persistence of parasites in scarred tissue. Although lupoid leishmaniasis (LL) has been used as a synonym of LRC, a clear difference between LRC and LL can be defined as LL is the initial clinical presentation while LRC is a recurrent lesion. The results indicate that it is not appropriate to use these two denominations as synonyms. The designation of LRC should be maintained in order to define recidives occurring at the border of an old scar of cutaneous leishmaniasis, avoiding the confusion with the lupoid form of the disease.
To describe American cutaneous leishmaniasis of the eyelids and highlight the main clinical and d... more To describe American cutaneous leishmaniasis of the eyelids and highlight the main clinical and diagnostic features of lesions, which are rare in this location. Retrospective, noncomparative case series Leishmanin skin test, touch preparations, histopathologic analysis, and culture in appropriate media were used for clinical confirmation and parasitologic diagnosis. Positive cultures were identified by the iso-enzymes technique. All patients were treated with pentavalent antimony applied intramuscularly. Leishmanin skin test was positive in all five patients. Touch preparations, histopathologic analysis, and culture were performed in four patients. Touch preparations were positive (presence of Leishman's bodies) in two patients; histopathologic analysis showed a granulomatous infiltrate in four patients and parasite was present in two patients; culture was positive in three patients, and in two the parasite was identified as Leishmania (Viannia) braziliensis. Therapy was effective for all patients. Cutaneous leishmaniasis of the eyelids is uncommon in the Americas. The disease may present diagnostic difficulties when appearing in nonendemic areas. The clues for diagnosis are the clinical aspect of lesions, the epidemiologic data, and a positive Leishmanin skin test. Demonstration of parasite is not always possible. Pentavalent antimonial compounds are the therapy of choice. Formerly, transmission of leishmaniasis occurred only when humans penetrated forested areas and became an incidental host. Now, eyelid lesions are part of the changing pattern in the transmission of the disease. With the increase in ecotourism, these lesions may begin to be seen in air travelers returning to other parts of the world.
Revista Do Instituto De Medicina Tropical De Sao Paulo, 2000
Response to treatment with antimonial drugs varies considerably depending on the parasite strain ... more Response to treatment with antimonial drugs varies considerably depending on the parasite strain involved, immune status of the patient and clinical form of the disease. Therapeutic regimens with this first line drug have been frequently modified both, in dose and duration of therapy. A regimen of 20 mg/kg/day of pentavalent antimony (Sb5+) during four weeks without an upper limit on the daily dose is currently recommended for mucosal disease ("espundia"). Side-effects with this dose are more marked in elderly patients, more commonly affected by this form of leishmaniasis. According to our experience, leishmaniasis in Rio de Janeiro responds well to antimony and, in cutaneous disease, high cure rates are obtained with 5 mg/kg/day of Sb5+ during 30 to 45-days. In this study a high rate of cure (91.4%) employing this dose was achieved in 36 patients with mild disease in this same geographic region. Side-effects were reduced and no antimony refractoriness was noted with subsequent use of larger dose in patients that failed to respond to initial schedule.
The host response to infection appears to be regulated by specific patterns of local cytokine pro... more The host response to infection appears to be regulated by specific patterns of local cytokine production. In the mouse, resistance to many pathogens including Leishmania is associated with a THl cytokine profile, IL-2 and IFN-,y; whereas susceptibility to infection is associated with production of TH2 cytokines, IL4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-y, and lymphotoxin were relatively predominant. In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production. (J. Clin. Invest. 1993.
Cutaneous leishmaniasis is endemic in the tropics and neotropics. It is often referred to as a gr... more Cutaneous leishmaniasis is endemic in the tropics and neotropics. It is often referred to as a group of diseases because of the varied spectrum of clinical manifestations, which range from small cutaneous nodules to gross mucosal tissue destruction. Cutaneous leishmaniasis can be caused by several Leishmania spp and is transmitted to human beings and animals by sandfl ies. Despite its increasing worldwide incidence, but because it is rarely fatal, cutaneous leishmaniasis has become one of the so-called neglected diseases, with little interest by fi nancial donors, public-health authorities, and professionals to implement activities to research, prevent, or control the disease. In endemic countries, diagnosis is often made clinically and, if possible, by microscopic examination of lesion biopsy smears to visually confi rm leishmania parasites as the cause. The use of more sophisticated diagnostic techniques that allow for species identifi cation is usually restricted to research or clinical settings in non-endemic countries. The mainstays of cutaneous leishmaniasis treatment are pentavalent antimonials, with new oral and topical treatment alternatives only becoming available within the past few years; a vaccine currently does not exist. Disease prevention and control are diffi cult because of the complexity of cutaneous leishmaniasis epizoology, and the few options available for eff ective vector control.
Four mongrel dogs were intradermically inoculated with 3 x 10(6) Leishmania braziliensis brazilie... more Four mongrel dogs were intradermically inoculated with 3 x 10(6) Leishmania braziliensis braziliensis promastigotes. Three out of the four animals developed cutaneous lesions respectively 4, 7, and 8 months after. The fourth dog did not develop lesion at the inoculation site, but a mucosal ulcer was seen 16 months after the inoculum. Clinical, histopathological, and serological findings were similar to what is found in natural canine infection as well as in the human disease. These results suggest that dogs may be an useful model for L. b. braziliensis infection.
Journal of The European Academy of Dermatology and Venereology, 1998
AbstractObjectiveA report of four cases of American cutaneous leishmaniasis associated with HIV i... more AbstractObjectiveA report of four cases of American cutaneous leishmaniasis associated with HIV infection is presented.A report of four cases of American cutaneous leishmaniasis associated with HIV infection is presented.BackgroundThe association of mucocutaneous leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the literature thus far.The association of mucocutaneous leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the literature thus far.SubjectsFour new cases are described and the differences between the clinical presentation in immunocompromised and immunocompetent patients are emphasized.Four new cases are described and the differences between the clinical presentation in immunocompromised and immunocompetent patients are emphasized.ConclusionsMultiple cutaneous lesions plus mucosal involvement characterize the clinical presentation of American cutaneous leishmaniasis in association with HIV infection in the majority of the cases. A serological investigation for HIV infection is recommended for patients presenting with this type of clinical picture, especially if the patient is a young male.Multiple cutaneous lesions plus mucosal involvement characterize the clinical presentation of American cutaneous leishmaniasis in association with HIV infection in the majority of the cases. A serological investigation for HIV infection is recommended for patients presenting with this type of clinical picture, especially if the patient is a young male.
The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were ... more The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were made to characterize the evolution of different parasite strains and the immune responses they elicited in this experimental host. A standardized inoculum of promastigotes was injected intradermally either above the eyelid or on the forearm of each monkey. Sixteen infected monkeys developed longstanding infections which lasted until the end of the observation period (33 months). The time required for lesion development was very variable, not only for the isolates showing molecular differences but also for individual animals in groups infected with the same parasite strain. The inocula produced lesions of variable severity, ranging from localized cutaneous leishmaniasis (CL) with a tendency to spontaneous healing to non-healing disease. One infected animal developed persistent metastatic skin and mucosal lesions. Anti-Leishmania antibodies and parasite-specific T-cell responses were induced by the experimental infections. As the granulomatous inflammatory response found at the lesions in L. (V.) braziliensis-infected M. mulatta was similar to that in patients with CL, this primate model could be useful for studying the pathophysiology and immunoregulatory events associated with disease evolution, as well as for the evaluation of new drugs or candidate vaccines.
Human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in p... more Human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in previous reports. Seroprevalence of antibodies to Leishmania donovani was shown to be related to prior blood transfusions in multiply transfused hemodialysis patients in Natal, Rio Grande do Norte, Brazil. In this study, a possible correlation between seroreactivity and the presence of L. donovani DNA was investigated in asymptomatic healthy blood donors. Sera were tested using the fucose mannose ligand (FML) ELISA, which was shown to have a sensitivity of 100%, a specificity of 96-100%, reliability, and diagnostic and prognostic potential for the detection of human and canine kala-azar, respectively. Leishmanial DNA was assessed by the polymerase chain reaction (PCR) and dotblot hybridization techniques in blood and bone marrow samples. Among 21 FML-seroreactive asymptomatic blood donors, 5 (24%) were positive by the PCR and 9 (43%) were positive in a dot-blot assay of blood samples, showing a significant correlation ( 2 ϭ 14.24, P Ͻ 0.01). No Leishmania DNA was detected in 20 FML non-reactive blood donors. Our results point to the need for control of transmission of kala-azar by blood transfusion in areas endemic for this disease.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2002
A long-term evaluation of human American tegumentary leishmaniasis patients was conducted to dete... more A long-term evaluation of human American tegumentary leishmaniasis patients was conducted to detect immunological and/or parasitological indicators associated with cure or protection against leishmaniasis. Cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients from endemic areas of Leishmania braziliensis infection in Brazil were studied during the active disease, at the end of therapy, and up to 10 years after the end of therapy. For immunological studies, lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ T cells reactive to L. braziliensis and cytokine production in vitro were assayed. In CL, with its tendency for healing lesions, at or shortly after the completion of therapy the ratio of CD4+ to CDS+ T cells was approximately one and production of interferon y (IFN,) remainded roughly constant. In ML, these apparently beneficial CD4+/CD8+ ratios and cytokine patterns appeared later. The long-term memory T cell responses were associated with preferential induction of CD4' subpopulations and IFNy production that probably led to protection against relapses or reinfection. Deoxyribonucleic acid (DNA) was isolated from peripheral blood and oligonucleotides that amplify the conserved region of the minicircle molecules of Leishmania were used in a 'hot-start' polymerase chain reaction (PCR). Leishmania DNA was found in about one-quarter of the patients with active disease as well as in individuals who had received chemotherapy. The PCR was also positive in one-third of the individuals with a positive skin test but no past or present history of leishmaniasis.
Background Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasi... more Background Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis.
Journal of The European Academy of Dermatology and Venereology, 1998
AbstractBackgroundLeishmaniasis is an important protozoan disease. In the Americas it is produced... more AbstractBackgroundLeishmaniasis is an important protozoan disease. In the Americas it is produced by several species of the genus Leishmania, transmitted by sand flies of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more serious involvement of oronasal mucosa that may progress to destruction of central structures of the face and to the life-threatening visceral forms. Leishmania Viannia braziliensis is the most widespread species in Brazil and is often associated with mucosal involvement. Cutaneous lesions are commonly localised in uncovered areas of the body. Genital lesions are rare.Leishmaniasis is an important protozoan disease. In the Americas it is produced by several species of the genus Leishmania, transmitted by sand flies of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more serious involvement of oronasal mucosa that may progress to destruction of central structures of the face and to the life-threatening visceral forms. Leishmania Viannia braziliensis is the most widespread species in Brazil and is often associated with mucosal involvement. Cutaneous lesions are commonly localised in uncovered areas of the body. Genital lesions are rare.Materials and methodsA patient with an ulcerated lesion of the glans penis, followed subsequently by mucosal lesions of the nasal cavity and palate, is presented. Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy of the ulcer border processed for histopathological examination and culture in NNN medium.A patient with an ulcerated lesion of the glans penis, followed subsequently by mucosal lesions of the nasal cavity and palate, is presented. Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy of the ulcer border processed for histopathological examination and culture in NNN medium.ResultsLeishmanin skin test was positive. Histopathology showed a granulomatous infiltrate containing some parasites. Culture was positive for Leishmania sp., and was later identified by zymodeme analysis and monoclonal antibodies as L.(V.)braziliensis. The patient was treated with pentavalent antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.Leishmanin skin test was positive. Histopathology showed a granulomatous infiltrate containing some parasites. Culture was positive for Leishmania sp., and was later identified by zymodeme analysis and monoclonal antibodies as L.(V.)braziliensis. The patient was treated with pentavalent antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.Comments and conclusionsIn men, especially over 50 years of age, ulceration of the glans penis is highly suggestive of carcinoma. Precise differential diagnosis is imperative. A lesion, such as the one reported, may cause diagnostic difficulties when it presents in countries different from the source, where the condition is very uncommon. This is increasingly frequent in the current era of widespread air travel.In men, especially over 50 years of age, ulceration of the glans penis is highly suggestive of carcinoma. Precise differential diagnosis is imperative. A lesion, such as the one reported, may cause diagnostic difficulties when it presents in countries different from the source, where the condition is very uncommon. This is increasingly frequent in the current era of widespread air travel.
A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braz... more A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braziliensis reactive T cells (Lbb-T cells) in peripheral blood and in the lesions of patients with mild localized cutaneous leishmaniasis (LCL) or with severe mucosal leishmaniasis (MCL). The frequencies of Lbb-T cells in peripheral blood varied from 1:107 300 to 1:3587 and were not significantly different in MCL and LCL patients. However, a significant difference was encountered (P <0.02) between the T cells frequencies in cutaneous (1:748 to 1:45) and mucosal lesions (1:152 to 1:13). A positive correlation was also observed between these frequencies and the magnitude of delayed-type hypersensitivity (DTH) (P < 0.01) and the presence of fibrinoid necrosis and granulomatous reaction in the site of the lesions (P<0.05). The lack of correlation between the severity of disease (MCL or LCL) and the frequency of Lbb-T cells in peripheral blood gave no indications towards understanding the physiopathology of severe or mild disease. However, the correlation between high T cell frequencies in the site of the lesions, the magnitude of DTH, the fibrinoid necrosis and the severity of the disease (MCL lesions) points to the possibility that the presence of a strong T cell dependent cellular immune response in the site of the lesions may have a deleterious effect. However, a local well modulated T cell immune response might provide healing of the lesions.
The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under con... more The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side-effects. In this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis. Seventy-four patients from Rio de Janeiro state, Brazil, and presenting with single ulcerative cutaneous lesions mainly located on the trunk or extremities were enrolled in the study. The drug employed was N-methyl glucamine (425 mg of Sbv in each 5 ml ampoule). Each lesion was infiltrated with the drug at the four cardinal points in order to achieve complete blanching. Of the 74 patients, 59 (80%) were healed after a 12-week interval. Extensive follow-up (up to 10 years) disclosed no relapses or the development of mucosal lesions. The aim of therapy in New World cutaneous leishmaniasis is the healing of the cutaneous lesion and the prevention of late mucosal damage. Both conditions were achieved with the treatment employed with no side-effects and a considerable decrease in costs. In addition, the method is easy to apply in the field.
Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical f... more Localized Cutaneous Leishmaniasis (LCL) and Mucosal Leishmaniasis (ML) are two extreme clinical forms of American Tegumentary Leishmaniasis that usually begin as solitary primary cutaneous lesions. Host and parasite factors that influence the progression of LCL to ML are not completely understood. In this manuscript, we compare the gene expression profiles of primary cutaneous lesions from patients who eventually developed ML to those that did not. Using RNA-seq, we analyzed both the human and Leishmania transcriptomes in primary cutaneous lesions. Limited number of reads mapping to Leishmania transcripts were obtained. For human transcripts, compared to ML patients, lesions from LCL patients displayed a general multi-polarization of the adaptive immune response and showed up-regulation of genes involved in chemoattraction of innate immune cells and in antigen presentation. We also identified a potential transcriptional signature in the primary lesions that may predict long-term disease outcome. We were able to simultaneously sequence both human and Leishmania mRNA transcripts in primary cutaneous leishmaniasis lesions. Our results suggest an intrinsic difference in the immune capacity of LCL and ML patients. The findings correlate the complete cure of L. braziliensis infection with a controlled inflammatory response and a balanced activation of innate and adaptive immunity.
The technique of polymerase chain reaction (PCR) associated to hybridization was used to screen 1... more The technique of polymerase chain reaction (PCR) associated to hybridization was used to screen 123 samples collected from wild and synanthropic rodents captured in a cutaneous and visceral leishmaniasis endemic area in the State of Minas Gerais, Brazil. The detection of Leishmania spp in naturally infected rodents is of fundamental importance for incriminating them as possible reservoir hosts of the diseases in Minas Gerais. A total of 62 specimens belonging to wild (Thrichomys apereoides, Oryzomys subflavus, Galea spixii, Bolomys lasiurus and Wiedomys pyrrhorhinos) and synanthropic (R. rattus) rodent species were captured in different ecotopes. Blood and skin samples were submitted for PCR analyses followed by molecular hybridization with specific probes for the three Leishmania-species complexes. Fifteen samples were found positive after PCRhybridization and identified as follows: nine belonging to the L. mexicana complex, three to the L. braziliensis complex and three to the L. donovani complex. Positive PCR results were found in 11 out of the 61 (18%) blood samples and in four out of the 62 (6.4%) skin fragments screened. R. rattus and T. apereoides were the most abundant species in the area also presenting high prevalence of natural infection. The presence of parasite DNA belonging to L. braziliensis, L. mexicana and L. donovani complexes was confirmed in several individuals of a rodent species, R. rattus. This work is the first report of the detection of L.
Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease... more Leprosy provides a useful model for understanding immunoregulatory mechanisms in man. The disease forms a spectrum in which the immunologic response of the patient correlates with the clinical and histopathologic classification (1-3). At one end of the spectrum, patients with tuberculoid leprosy have one or several skin lesions in which bacilli can rarely be identified . CD4+ T lymphocytes predominate in these lesions (4-7) and respond to Mycobacterium leßrae in vitro (8). At the other end of the spectrum, patients with lepromatous leprosy have diffuse infiltration of skin and nerves with bacilli-laden macrophages. CD8+ cells predominate in lepromatous lesions and function as antigen-specific Ts cells in vitro (9, 10). The CD4+ lymphocytes derived from these lesions are unresponsive to M. leßrae . Imposed upon this spectrum are the so-called "reactional states" of reversal reaction and erythema nodosum leprosum (ENL)' that are of immunologic interest in understanding mechanisms of immunoregulation in man.
Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been... more Leishmaniasis recidiva cutis (LRC) is rare in New World leishmaniasis. Only seven cases have been reported so far. Four cases are reported here. Parasite diagnosis was performed by classical methods of touch preparations, histopathologic sections, and cultures. In addition, the detection of parasite DNA by the polymerase chain reaction (PCR) was performed in all cases. Parasites were detected by at least one of the classical methods in all primary lesions; however, only the PCR was positive in the recidivant lesions. LRC cases most likely represent a reactivation of an initial infection, probably due to the persistence of parasites in scarred tissue. Although lupoid leishmaniasis (LL) has been used as a synonym of LRC, a clear difference between LRC and LL can be defined as LL is the initial clinical presentation while LRC is a recurrent lesion. The results indicate that it is not appropriate to use these two denominations as synonyms. The designation of LRC should be maintained in order to define recidives occurring at the border of an old scar of cutaneous leishmaniasis, avoiding the confusion with the lupoid form of the disease.
To describe American cutaneous leishmaniasis of the eyelids and highlight the main clinical and d... more To describe American cutaneous leishmaniasis of the eyelids and highlight the main clinical and diagnostic features of lesions, which are rare in this location. Retrospective, noncomparative case series Leishmanin skin test, touch preparations, histopathologic analysis, and culture in appropriate media were used for clinical confirmation and parasitologic diagnosis. Positive cultures were identified by the iso-enzymes technique. All patients were treated with pentavalent antimony applied intramuscularly. Leishmanin skin test was positive in all five patients. Touch preparations, histopathologic analysis, and culture were performed in four patients. Touch preparations were positive (presence of Leishman&amp;amp;#39;s bodies) in two patients; histopathologic analysis showed a granulomatous infiltrate in four patients and parasite was present in two patients; culture was positive in three patients, and in two the parasite was identified as Leishmania (Viannia) braziliensis. Therapy was effective for all patients. Cutaneous leishmaniasis of the eyelids is uncommon in the Americas. The disease may present diagnostic difficulties when appearing in nonendemic areas. The clues for diagnosis are the clinical aspect of lesions, the epidemiologic data, and a positive Leishmanin skin test. Demonstration of parasite is not always possible. Pentavalent antimonial compounds are the therapy of choice. Formerly, transmission of leishmaniasis occurred only when humans penetrated forested areas and became an incidental host. Now, eyelid lesions are part of the changing pattern in the transmission of the disease. With the increase in ecotourism, these lesions may begin to be seen in air travelers returning to other parts of the world.
Revista Do Instituto De Medicina Tropical De Sao Paulo, 2000
Response to treatment with antimonial drugs varies considerably depending on the parasite strain ... more Response to treatment with antimonial drugs varies considerably depending on the parasite strain involved, immune status of the patient and clinical form of the disease. Therapeutic regimens with this first line drug have been frequently modified both, in dose and duration of therapy. A regimen of 20 mg/kg/day of pentavalent antimony (Sb5+) during four weeks without an upper limit on the daily dose is currently recommended for mucosal disease (&amp;amp;amp;amp;quot;espundia&amp;amp;amp;amp;quot;). Side-effects with this dose are more marked in elderly patients, more commonly affected by this form of leishmaniasis. According to our experience, leishmaniasis in Rio de Janeiro responds well to antimony and, in cutaneous disease, high cure rates are obtained with 5 mg/kg/day of Sb5+ during 30 to 45-days. In this study a high rate of cure (91.4%) employing this dose was achieved in 36 patients with mild disease in this same geographic region. Side-effects were reduced and no antimony refractoriness was noted with subsequent use of larger dose in patients that failed to respond to initial schedule.
The host response to infection appears to be regulated by specific patterns of local cytokine pro... more The host response to infection appears to be regulated by specific patterns of local cytokine production. In the mouse, resistance to many pathogens including Leishmania is associated with a THl cytokine profile, IL-2 and IFN-,y; whereas susceptibility to infection is associated with production of TH2 cytokines, IL4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-y, and lymphotoxin were relatively predominant. In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production. (J. Clin. Invest. 1993.
Cutaneous leishmaniasis is endemic in the tropics and neotropics. It is often referred to as a gr... more Cutaneous leishmaniasis is endemic in the tropics and neotropics. It is often referred to as a group of diseases because of the varied spectrum of clinical manifestations, which range from small cutaneous nodules to gross mucosal tissue destruction. Cutaneous leishmaniasis can be caused by several Leishmania spp and is transmitted to human beings and animals by sandfl ies. Despite its increasing worldwide incidence, but because it is rarely fatal, cutaneous leishmaniasis has become one of the so-called neglected diseases, with little interest by fi nancial donors, public-health authorities, and professionals to implement activities to research, prevent, or control the disease. In endemic countries, diagnosis is often made clinically and, if possible, by microscopic examination of lesion biopsy smears to visually confi rm leishmania parasites as the cause. The use of more sophisticated diagnostic techniques that allow for species identifi cation is usually restricted to research or clinical settings in non-endemic countries. The mainstays of cutaneous leishmaniasis treatment are pentavalent antimonials, with new oral and topical treatment alternatives only becoming available within the past few years; a vaccine currently does not exist. Disease prevention and control are diffi cult because of the complexity of cutaneous leishmaniasis epizoology, and the few options available for eff ective vector control.
Four mongrel dogs were intradermically inoculated with 3 x 10(6) Leishmania braziliensis brazilie... more Four mongrel dogs were intradermically inoculated with 3 x 10(6) Leishmania braziliensis braziliensis promastigotes. Three out of the four animals developed cutaneous lesions respectively 4, 7, and 8 months after. The fourth dog did not develop lesion at the inoculation site, but a mucosal ulcer was seen 16 months after the inoculum. Clinical, histopathological, and serological findings were similar to what is found in natural canine infection as well as in the human disease. These results suggest that dogs may be an useful model for L. b. braziliensis infection.
Journal of The European Academy of Dermatology and Venereology, 1998
AbstractObjectiveA report of four cases of American cutaneous leishmaniasis associated with HIV i... more AbstractObjectiveA report of four cases of American cutaneous leishmaniasis associated with HIV infection is presented.A report of four cases of American cutaneous leishmaniasis associated with HIV infection is presented.BackgroundThe association of mucocutaneous leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the literature thus far.The association of mucocutaneous leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the literature thus far.SubjectsFour new cases are described and the differences between the clinical presentation in immunocompromised and immunocompetent patients are emphasized.Four new cases are described and the differences between the clinical presentation in immunocompromised and immunocompetent patients are emphasized.ConclusionsMultiple cutaneous lesions plus mucosal involvement characterize the clinical presentation of American cutaneous leishmaniasis in association with HIV infection in the majority of the cases. A serological investigation for HIV infection is recommended for patients presenting with this type of clinical picture, especially if the patient is a young male.Multiple cutaneous lesions plus mucosal involvement characterize the clinical presentation of American cutaneous leishmaniasis in association with HIV infection in the majority of the cases. A serological investigation for HIV infection is recommended for patients presenting with this type of clinical picture, especially if the patient is a young male.
The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were ... more The present studies on infections with Leishmania (Viannia) braziliensis in rhesus macaques were made to characterize the evolution of different parasite strains and the immune responses they elicited in this experimental host. A standardized inoculum of promastigotes was injected intradermally either above the eyelid or on the forearm of each monkey. Sixteen infected monkeys developed longstanding infections which lasted until the end of the observation period (33 months). The time required for lesion development was very variable, not only for the isolates showing molecular differences but also for individual animals in groups infected with the same parasite strain. The inocula produced lesions of variable severity, ranging from localized cutaneous leishmaniasis (CL) with a tendency to spontaneous healing to non-healing disease. One infected animal developed persistent metastatic skin and mucosal lesions. Anti-Leishmania antibodies and parasite-specific T-cell responses were induced by the experimental infections. As the granulomatous inflammatory response found at the lesions in L. (V.) braziliensis-infected M. mulatta was similar to that in patients with CL, this primate model could be useful for studying the pathophysiology and immunoregulatory events associated with disease evolution, as well as for the evaluation of new drugs or candidate vaccines.
Human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in p... more Human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in previous reports. Seroprevalence of antibodies to Leishmania donovani was shown to be related to prior blood transfusions in multiply transfused hemodialysis patients in Natal, Rio Grande do Norte, Brazil. In this study, a possible correlation between seroreactivity and the presence of L. donovani DNA was investigated in asymptomatic healthy blood donors. Sera were tested using the fucose mannose ligand (FML) ELISA, which was shown to have a sensitivity of 100%, a specificity of 96-100%, reliability, and diagnostic and prognostic potential for the detection of human and canine kala-azar, respectively. Leishmanial DNA was assessed by the polymerase chain reaction (PCR) and dotblot hybridization techniques in blood and bone marrow samples. Among 21 FML-seroreactive asymptomatic blood donors, 5 (24%) were positive by the PCR and 9 (43%) were positive in a dot-blot assay of blood samples, showing a significant correlation ( 2 ϭ 14.24, P Ͻ 0.01). No Leishmania DNA was detected in 20 FML non-reactive blood donors. Our results point to the need for control of transmission of kala-azar by blood transfusion in areas endemic for this disease.
Transactions of The Royal Society of Tropical Medicine and Hygiene, 2002
A long-term evaluation of human American tegumentary leishmaniasis patients was conducted to dete... more A long-term evaluation of human American tegumentary leishmaniasis patients was conducted to detect immunological and/or parasitological indicators associated with cure or protection against leishmaniasis. Cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients from endemic areas of Leishmania braziliensis infection in Brazil were studied during the active disease, at the end of therapy, and up to 10 years after the end of therapy. For immunological studies, lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ T cells reactive to L. braziliensis and cytokine production in vitro were assayed. In CL, with its tendency for healing lesions, at or shortly after the completion of therapy the ratio of CD4+ to CDS+ T cells was approximately one and production of interferon y (IFN,) remainded roughly constant. In ML, these apparently beneficial CD4+/CD8+ ratios and cytokine patterns appeared later. The long-term memory T cell responses were associated with preferential induction of CD4' subpopulations and IFNy production that probably led to protection against relapses or reinfection. Deoxyribonucleic acid (DNA) was isolated from peripheral blood and oligonucleotides that amplify the conserved region of the minicircle molecules of Leishmania were used in a 'hot-start' polymerase chain reaction (PCR). Leishmania DNA was found in about one-quarter of the patients with active disease as well as in individuals who had received chemotherapy. The PCR was also positive in one-third of the individuals with a positive skin test but no past or present history of leishmaniasis.
Background Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasi... more Background Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis.
Journal of The European Academy of Dermatology and Venereology, 1998
AbstractBackgroundLeishmaniasis is an important protozoan disease. In the Americas it is produced... more AbstractBackgroundLeishmaniasis is an important protozoan disease. In the Americas it is produced by several species of the genus Leishmania, transmitted by sand flies of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more serious involvement of oronasal mucosa that may progress to destruction of central structures of the face and to the life-threatening visceral forms. Leishmania Viannia braziliensis is the most widespread species in Brazil and is often associated with mucosal involvement. Cutaneous lesions are commonly localised in uncovered areas of the body. Genital lesions are rare.Leishmaniasis is an important protozoan disease. In the Americas it is produced by several species of the genus Leishmania, transmitted by sand flies of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more serious involvement of oronasal mucosa that may progress to destruction of central structures of the face and to the life-threatening visceral forms. Leishmania Viannia braziliensis is the most widespread species in Brazil and is often associated with mucosal involvement. Cutaneous lesions are commonly localised in uncovered areas of the body. Genital lesions are rare.Materials and methodsA patient with an ulcerated lesion of the glans penis, followed subsequently by mucosal lesions of the nasal cavity and palate, is presented. Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy of the ulcer border processed for histopathological examination and culture in NNN medium.A patient with an ulcerated lesion of the glans penis, followed subsequently by mucosal lesions of the nasal cavity and palate, is presented. Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy of the ulcer border processed for histopathological examination and culture in NNN medium.ResultsLeishmanin skin test was positive. Histopathology showed a granulomatous infiltrate containing some parasites. Culture was positive for Leishmania sp., and was later identified by zymodeme analysis and monoclonal antibodies as L.(V.)braziliensis. The patient was treated with pentavalent antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.Leishmanin skin test was positive. Histopathology showed a granulomatous infiltrate containing some parasites. Culture was positive for Leishmania sp., and was later identified by zymodeme analysis and monoclonal antibodies as L.(V.)braziliensis. The patient was treated with pentavalent antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed.Comments and conclusionsIn men, especially over 50 years of age, ulceration of the glans penis is highly suggestive of carcinoma. Precise differential diagnosis is imperative. A lesion, such as the one reported, may cause diagnostic difficulties when it presents in countries different from the source, where the condition is very uncommon. This is increasingly frequent in the current era of widespread air travel.In men, especially over 50 years of age, ulceration of the glans penis is highly suggestive of carcinoma. Precise differential diagnosis is imperative. A lesion, such as the one reported, may cause diagnostic difficulties when it presents in countries different from the source, where the condition is very uncommon. This is increasingly frequent in the current era of widespread air travel.
A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braz... more A limiting dilution analysis (LDA) was utilized to estimate the frequency of L. braziliensis braziliensis reactive T cells (Lbb-T cells) in peripheral blood and in the lesions of patients with mild localized cutaneous leishmaniasis (LCL) or with severe mucosal leishmaniasis (MCL). The frequencies of Lbb-T cells in peripheral blood varied from 1:107 300 to 1:3587 and were not significantly different in MCL and LCL patients. However, a significant difference was encountered (P <0.02) between the T cells frequencies in cutaneous (1:748 to 1:45) and mucosal lesions (1:152 to 1:13). A positive correlation was also observed between these frequencies and the magnitude of delayed-type hypersensitivity (DTH) (P < 0.01) and the presence of fibrinoid necrosis and granulomatous reaction in the site of the lesions (P<0.05). The lack of correlation between the severity of disease (MCL or LCL) and the frequency of Lbb-T cells in peripheral blood gave no indications towards understanding the physiopathology of severe or mild disease. However, the correlation between high T cell frequencies in the site of the lesions, the magnitude of DTH, the fibrinoid necrosis and the severity of the disease (MCL lesions) points to the possibility that the presence of a strong T cell dependent cellular immune response in the site of the lesions may have a deleterious effect. However, a local well modulated T cell immune response might provide healing of the lesions.
The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under con... more The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side-effects. In this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis. Seventy-four patients from Rio de Janeiro state, Brazil, and presenting with single ulcerative cutaneous lesions mainly located on the trunk or extremities were enrolled in the study. The drug employed was N-methyl glucamine (425 mg of Sbv in each 5 ml ampoule). Each lesion was infiltrated with the drug at the four cardinal points in order to achieve complete blanching. Of the 74 patients, 59 (80%) were healed after a 12-week interval. Extensive follow-up (up to 10 years) disclosed no relapses or the development of mucosal lesions. The aim of therapy in New World cutaneous leishmaniasis is the healing of the cutaneous lesion and the prevention of late mucosal damage. Both conditions were achieved with the treatment employed with no side-effects and a considerable decrease in costs. In addition, the method is easy to apply in the field.
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Papers by Claude Pirmez