Gabriel Grimaldi Jr. é atualmente pesquisador Emérito no Instituto Gonçalo Moniz, FIOCRUZ Bahia (Salvador, Brasil). Graduado em medicina humana (1972) e Mestre em Patologia Experimental (1976) pela UFBA. Doutor em Ciência, área de atuação: Microbiologia/Imunologia (1987) pela UFRJ. Realizou projetos de pós-graduação no Institute Pasteur de Lyon, França (1973-1974) e na Harvard Medical School, Boston-MS (1981-1983) e de pós-doutoramento na Yale University, New Heaven-CT (1986-1993).
Revista do Instituto de Medicina Tropical de São 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 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.
In this study, we have analysed enzyme polymorphism among a group of protozoan parasites of the g... more In this study, we have analysed enzyme polymorphism among a group of protozoan parasites of the genus Endotrypanum (Kinetoplastida: Trypanosomatidae). Seventeen stocks of Endotrypanum spp. isolated from sloths (Choloepus didactylus and C. juruanus) in the Amazon Region of Brazil were analysed by enzyme electrophoresis, and their electromorphic profiles were compared with reference strains reported previously. The 16 enzymic loci were analysed, and the strains were classified into zymodemes, each representing parasites with unique enzyme profiles. Each zymodeme was considered as an elementary taxon, and using numerical analyses (cladistic, agglomerative hierarchical and ordination techniques) the genus was shown to be monophyletic and the 12 zymodemes characterized could be divided into 3 groups (A, B, C). The heterogeneous population (which may represent a complex of parasite species or strains variants) showed, however, no correlation with the origin (i.e. host species involved or geographic area of isolation) of Endotrypanum stocks. Eight isolates of Endotrypanum sp. from Rondônia State (Brazil) and a parasite strain from Panama were clustered together into a zymodeme, which was phenetically closely related to the E. monterogeii from Costa Rica. The data indicate that E. schaudinni is a species complex.
In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better und... more In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leishmania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long-term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1-mediated, immunity-induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1-cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections.
Revista do Instituto de Medicina Tropical de São 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 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.
In this study, we have analysed enzyme polymorphism among a group of protozoan parasites of the g... more In this study, we have analysed enzyme polymorphism among a group of protozoan parasites of the genus Endotrypanum (Kinetoplastida: Trypanosomatidae). Seventeen stocks of Endotrypanum spp. isolated from sloths (Choloepus didactylus and C. juruanus) in the Amazon Region of Brazil were analysed by enzyme electrophoresis, and their electromorphic profiles were compared with reference strains reported previously. The 16 enzymic loci were analysed, and the strains were classified into zymodemes, each representing parasites with unique enzyme profiles. Each zymodeme was considered as an elementary taxon, and using numerical analyses (cladistic, agglomerative hierarchical and ordination techniques) the genus was shown to be monophyletic and the 12 zymodemes characterized could be divided into 3 groups (A, B, C). The heterogeneous population (which may represent a complex of parasite species or strains variants) showed, however, no correlation with the origin (i.e. host species involved or geographic area of isolation) of Endotrypanum stocks. Eight isolates of Endotrypanum sp. from Rondônia State (Brazil) and a parasite strain from Panama were clustered together into a zymodeme, which was phenetically closely related to the E. monterogeii from Costa Rica. The data indicate that E. schaudinni is a species complex.
In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better und... more In order to unravel the physiopathology of leishmaniasis in humans, it is necessary to better understand how Leishmania are able to survive for years within immunologically active granulomas. In the present study, we used a macaque (Macaca mulatta) model of infection with Leishmania braziliensis as a means of assessing the usefulness of this primate system. This model more closely mirrors human protective immunity to Leishmania than the murine model; therefore, we used it to study the host inflammatory granulomatous response involved in the control of cutaneous leishmaniasis. Infected primates developed localized long-term skin ulcerations, but complete spontaneous clinical healing occurred in all infected animals. The infection induced the recruitment and activation of inflammatory mast cells, granulocytes, mononuclear phagocytes, and lymphocytes at the site of infection. During the acute reaction, polymorphonuclear leukocytes were more prominent than other cell types and apparently destroyed many parasites; macrophages then rapidly engulfed dying neutrophils together with their parasitic cargo. In the chronic phase, persisting parasites induced a typical T helper (Th) cytokine, type 1-mediated, immunity-induced granulomatous reaction. By this time, more or less differentiated macrophage accumulations were found, and these evolved to become mature tissue granulomas consisting of all the specific cell types found within human granulomas. In the healing stage, fibroblasts proliferated at the periphery and finally invaded the granulomas with fibrotic substitution. These findings point to the feasibility of using this model to elucidate the potentially disabling Th1-cell mechanisms that may eventually render the host granulomatous response inadequate for fighting L. braziliensis infections.
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