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Rev. Soc. Bras. Med. Trop ; 52: e20180323, 2019. graf
Article in English | LILACS | ID: biblio-1003132


Abstract We report the case of a 32-year-old man from Rio de Janeiro, who was infected in the Amazon region of Brazil by Leishmania (Viannia) naiffi. Generally, patients with L. naiffi cutaneous leishmaniasis exhibit a good therapeutic response to either pentavalent antimonials or pentamidine. However, after pentamidine treatment, this patient's infection evolved to therapeutic failure. To understand this clinical outcome, we investigated the presence of the Leishmania RNA virus (LRV) in parasites isolated from the cutaneous lesion; herein, we discuss the possible association between a poor response to pentamidine therapy and the presence of the LRV.

Humans , Male , Adult , Pentamidine/therapeutic use , RNA Viruses/genetics , Trypanocidal Agents/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Leishmania/virology , Pentamidine/adverse effects , Trypanocidal Agents/adverse effects , Polymerase Chain Reaction , Treatment Failure
Rev. Soc. Bras. Med. Trop ; 52: e20190315, 2019. tab, graf
Article in English | LILACS | ID: biblio-1057249


Abstract INTRODUCTION: Immunological control of Mycobacterium tuberculosis infection is dependent on the cellular immune response, mediated predominantly by Th1 type CD4+ T cells. Polarization of the immune response to Th2 can inhibit the host immune protection against pathogens. Patients with tuberculosis coinfected with helminths demonstrate more severe pulmonary symptoms, a deficiency in the immune response against tuberculosis, and an impaired response to anti-tuberculosis therapy. METHODS: We evaluated the cellular immune response and the impact of the presence of Ascaris lumbricoides on the immune and clinical response in pulmonary tuberculosis patients. Ninety-one individuals were included in the study: 38 tuberculosis patients, 11 tuberculosis patients coinfected with Ascaris lumbricoides and other helminths, 10 Ascaris lumbricoides patients, and 34 non-infected control individuals. Clinical evolution of pulmonary tuberculosis was studied on 0, 30, 60, and 90 days post-diagnosis of Mycobacterium tuberculosis and Ascaris lumbricoides. Furthermore, immune cells and plasma cytokine profiles were examined in mono/coinfection by Mycobacterium tuberculosis and Ascaris lumbricoides using flow cytometry. RESULTS: There were no statistical differences in any of the evaluated parameters and the results indicated that Ascaris lumbricoides infection does not lead to significant clinical repercussions in the presentation and evolution of pulmonary tuberculosis. CONCLUSIONS: The association with Ascaris lumbricoides did not influence the Th1, Th2, and Th17 type responses, or the proportions of T lymphocyte subpopulations. However, higher serum levels of IL-6 in tuberculosis patients may explain the pulmonary parenchymal damage.

Humans , Animals , Male , Female , Adult , Young Adult , Ascariasis/immunology , Tuberculosis, Pulmonary/immunology , Interleukin-6/blood , Ascaris lumbricoides , Ascariasis/complications , Time Factors , Tuberculosis, Pulmonary/complications , Antibodies, Helminth/blood , Case-Control Studies , Cytokines/immunology , Cytokines/blood , Interleukin-6/immunology , Disease Progression , Coinfection , Flow Cytometry , Middle Aged
Rev. Soc. Bras. Med. Trop ; 51(1): 111-114, Jan.-Feb. 2018. graf
Article in English | LILACS | ID: biblio-897041


Abstract The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process. Together with P. lutzii, P. brasiliensis appears to be involved in severe cases of PCM.

Humans , Male , Young Adult , Paracoccidioides/genetics , Paracoccidioidomycosis/complications , Paracoccidioidomycosis/diagnosis , Phylogeny , Shock, Septic/microbiology , Severity of Illness Index , Fatal Outcome , Immunocompetence
Mem. Inst. Oswaldo Cruz ; 111(5): 349-354, May 2016. graf
Article in English | LILACS | ID: lil-782047


During its life cycle Leishmania spp. face several stress conditions that can cause DNA damages. Base Excision Repair plays an important role in DNA maintenance and it is one of the most conserved mechanisms in all living organisms. DNA repair in trypanosomatids has been reported only for Old World Leishmania species. Here the AP endonuclease from Leishmania (L.) amazonensis was cloned, expressed in Escherichia coli mutants defective on the DNA repair machinery, that were submitted to different stress conditions, showing ability to survive in comparison to the triple null mutant parental strain BW535. Phylogenetic and multiple sequence analyses also confirmed that LAMAP belongs to the AP endonuclease class of proteins.

DNA Damage/genetics , DNA Repair/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , Escherichia coli/genetics , Leishmania braziliensis/genetics , Mutation/genetics , Amino Acid Sequence , Escherichia coli Proteins/genetics , Escherichia coli/enzymology , Molecular Sequence Data
Mem. Inst. Oswaldo Cruz ; 110(5): 596-605, Aug. 2015. tab, ilus
Article in English | LILACS | ID: lil-755895


In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+T-cells are associated with larger lesions.


Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , /immunology , Leishmaniasis, Cutaneous/immunology , Receptors, Antigen, T-Cell/immunology , T-Lymphocyte Subsets/immunology , Brazil , Lymphocyte Activation/immunology , Receptors, Antigen, T-Cell/analysis
Rev. Soc. Bras. Med. Trop ; 48(supl.1): 12-19, 2015. tab, graf
Article in English | LILACS | ID: lil-748358


This study evaluated the occurrence of American tegumentary leishmaniasis (ATL) in the State of Amazonas, Brazil, in the last 30 years with emphasis on the last 10 years (2001 to 2010). The disease was predominantly observed in males (76.2%), in the 21- to 30-year-old age group (26.6%) and in extractive workers (43.7%); 3.3% of the cases were the mucosal form. The endemic channel shows the disease seasonality, with a predominance of cases at the beginning and end of each year. The number of cases by municipality in the period of 2001-2010 shows the maintenance of the endemic in the localities where the highest numbers of cases have always been registered, namely, Manaus, Rio Preto da Eva, Itacoatiara and Presidente Figueiredo. The comparison of data from 2001 to 2005 and from 2006 to 2010 showed the emergence of this disease in municipalities that had been previously unaffected. In the last years, there has been a significant increase in the activities of control, diagnosis and treatment of leishmaniasis in the State of Amazonas. In conclusion, the historical series of ATL analyzed in this study suggests that the transmission foci remain and are even expanding, though without continuous transmission in the intra- or peridomicile settings. Moreover, the disease will persist in the Amazon while the factors associated with infection acquisition relative to forest exploitation continue to have economic appeal. There is a real expectation of wide variations in disease incidence that can be influenced by climate and economic aspects.

Animals , Female , Male , Gastropoda/genetics , Life Cycle Stages/genetics , Sexual Behavior, Animal , Sex Determination Processes/genetics , Fertilization , Genetic Variation , Genetics, Population , Genotype , Microsatellite Repeats/genetics , Paternity , Sex Characteristics
Mem. Inst. Oswaldo Cruz ; 107(8): 985-992, Dec. 2012. graf
Article in English | LILACS | ID: lil-660644


Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4+ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4+ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8+ and human leukocyte antigen-DR expression on CD3+ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.

Adult , Female , Humans , Male , Anemia/parasitology , /immunology , HIV Infections/immunology , Lymphocyte Activation/immunology , Malaria, Falciparum/immunology , Parasitemia/immunology , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/immunology , Case-Control Studies , Cross-Sectional Studies , HIV Infections/complications , Mozambique , Malaria, Falciparum/complications , Severity of Illness Index
Acta biol. colomb ; 16(3): 197-212, dic. 2011.
Article in Spanish | LILACS-Express | LILACS | ID: lil-635096


Há mais de 200 anos a vacinação tem sido uma ferramenta muito efetiva na prevenção de doenças infecciosas e juntamente com o saneamento básico, o efeito prático da vacinação pode ser considerado o maior benefício à saúde pública do século XX. No entanto, o desenvolvimento de vacinas permanece um objetivo importante no campo da imunologia e na última década observa-se uma mudança em direção a uma abordagem mais racional, baseada em uma compreensão molecular da patogenicidade microbiana, na utilização de novas tecnologias recombinantes e no desenvolvimento de sistemas de liberação de vacinas mais efetivos. Este trabalho descreve o progresso no desenvolvimento de vacinas a partir dos primeiros relatos das práticas de vacinação, passando pelo estado atual de desenvolvimento de vacinas, pelas novas estratégias vacinais e pelo impacto da vacinação no controle das doenças imunopreveníveis.

Desde hace más de 200 años la vacunación ha sido una herramienta efectiva en la prevención de enfermedades infecciosas junto con el saneamiento ambiental. El efecto práctico de la vacunación puede ser considerado como el mayor beneficio para la salud pública del siglo XX. Sin embargo, el desarrollo de vacunas sigue siendo un objetivo importante en inmunología y en la última década ha habido un cambio hacia un enfoque más racional, basada en los hallazgos moleculares de patogenia microbiana, el uso de nuevas tecnologías recombinantes y el desarrollo de sistemas de suministro de las vacunas más eficaces. En este trabajo se describen los progresos en el desarrollo de vacunas, partiendo de los primeros informes de prácticas de vacunación, hasta el estado actual del desarrollo de vacunas, las nuevas estrategias de vacunas y el impacto de la vacunación en el control de enfermedades prevenibles.

For over 200 years, vaccination has been a very effective tool to prevent infectious diseases along with sanitation. In practical terms, it can be considered the greatest public health benefit of the twentieth century. However, vaccine development remains as a developing domain in the field of immunology and in the last decade there has been a shift towards a more rational approach in vaccination design, based on a molecular understanding of microbial pathogenesis, the use of new recombinant technologies and the development of more effective delivery systems for vaccines. This paper describes the progress in vaccine development from the first reports of vaccination practices, through the current state of vaccine development, the new vaccine strategies and the impact of vaccination in the control of preventable diseases.

Mem. Inst. Oswaldo Cruz ; 105(5): 692-697, Aug. 2010. graf, tab
Article in English | LILACS | ID: lil-557232


An increase in morbidity associated with visceral leishmaniasis (VL) in human immunodeficiency virus (HIV)/AIDS patients has been described in Africa and the Mediterranean. Despite the high endemicity of VL and HIV-1/AIDS in Brazil, this association has not been thoroughly investigated. Our aim was to evaluate the epidemiologic and clinical characteristics of VL-HIV-1/AIDS cases from Central-west [Mato Grosso do Sul (MS)] Brazil. Medical records of 23 VL-HIV-1/AIDS patients were reviewed. Patients were predominantly adult males (87 percent) and 34.8 percent of the patients were intravenous drug users (IVDU). Leishmaniasis was the first opportunistic infection in 60 percent of the HIV-1 patients. Fever occurred in all patients, although splenomegaly and hepatomegaly were absent in 21.7 percent of the cases. CD4+ T-cell counts were below 200 cells/mm³ in 80 percent of the cases and the counts did not increase after clinical remission despite antiretroviral therapy. The first drug chosen to treat the cases was antimonial, but the therapeutic regimen was altered to amphotericin B in 12 of 17 cases due to side effects. Relapses were reported in 56.5 percent of the patients. IVDU may constitute an important risk factor for the transmission of both diseases in MS. VL-HIV-1/AIDS patients in MS share similar clinical characteristics as those from other endemic regions worldwide. Thus, these findings are critical for improving the surveillance of VL-HIV/AIDS patients.

Adult , Female , Humans , Male , Middle Aged , Young Adult , AIDS-Related Opportunistic Infections , Endemic Diseases , Leishmaniasis, Visceral , AIDS-Related Opportunistic Infections , AIDS-Related Opportunistic Infections , Amphotericin B , Antiprotozoal Agents , Brazil , Leishmaniasis, Visceral , Leishmaniasis, Visceral , Meglumine , Organometallic Compounds , Risk Factors , Viral Load
Rio de Janeiro; s.n; 1999. 144 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-507835


Foram obtidas células mononucleares das lesões (CML) e do sangue periférico (CMSP) de 40 pacientes com leishmaniose cutânea (LC), quatro com leishmaniose mucosa (LM) e quatro com leishmaniose disseminada (LDiss). As células foram caracterizadas por citofluorometria quanto ao fenótipo de linfócitos B, T, CD4+, CD8+, yo, macrófagos, receptor de IL-2 (IL-2R) e lFN-yR. As proporções de linfócitos T foram similares nos infiltrados de LC, LM e LDiss. Os percentuais de células CD4+ e CD8+ foram mais elevados nas lesões com tempo de evolução superior a três meses. Os casos de LM apresentaram percentuais mais elevados de células expressando IL-2R (X=87.2±5.2 percentil) e lFN-yR (X=81.3±6.6 percentil) quando comparados aos casos de LC e LDiss, podendo estar associado à gravidade das lesões mucosas. Foram realizados ensaios in vitro de resposta proliferativa de linfócitos (RPL) a antígenos de L. braziliensis (Ag-Lb), concanavalina A (Con-A), T. gondii (Ag-Tg) e T. cruzi (Ag-Tc). A RPL de CML a Ag-Lb foi positiva (índice de estimulação - IE ≥ 2.5 acima do controle) em 13 de 24 pacientes de LC (Δcpm 10-3=4.9±1.8). As CML de 10 em 16 pacientes de LC sororreativos ao Toxoplasma, proliferaram quando estimuladas com Ag-Tg (Δcpm 10-3=8.3±5). Por outro lado, CML de sete pacientes que não eram sororreagentes ao Toxoplasma, não proliferaram após estímulo com Ag-Tg. Apenas um paciente em 18 testados, apresentou RPL positiva (IE=3.4) a Ag-Tc. O sobrenadante destas culturas foi coletado para quantificação de citocinas do tipo 1 (IFN-y) e do tipo 2 (IL-4 e IL-5). O IFN-y foi detectado nas culturas de CML estimuladas com Con-A, Ag-Lb e Ag-Tg. Não foi detectada produção de IL-4 e IL-5 nestes sobrenadantes. O RANTES foi quantificado no sobrenadante de CML e de CMSP estimuladas com Ag-Lb. Células reativas a Ag-Lb estimuladas in vitro por quatro dias foram separadas em gradiente de Percoll e analisadas quanto ao fenótipo (CD4+ e CD8+). Os percentuais de células CD4+ e CD8+ reativas a Ag-Lb foram variáveis: três pacientes apresentaram CD4+ > CD8+ e três tiveram CD8+ > CD4+. Esses dados demonstram que linfócitos T de lesões de leishmaniose são capazes de proliferar e produzir IFN-y não apenas quando estimulados com antígenos de Leishmania, mas também após estímulo com outros antígenos não relacionados à infecção (Ex.:Tg). Logo, células reativas a outros antígenos também migram para as lesões de leishmaniose. O papel destas células para a cura ou agravamento da lesões ainda necessita ser determinado.

Humans , Cytokines , Leishmania , Leishmania braziliensis , Leishmaniasis, Cutaneous , Lymphocytes , Toxoplasma
Mem. Inst. Oswaldo Cruz ; 91(2): 225-9, Mar.-Apr. 1996. graf
Article in English | LILACS | ID: lil-174384


Tumor necrosis factor-alpha (TNF-alpha) is a cytokine produced by activated macrophages and other cells. In order to verify whether the serum levels of TNF-alpha in American tegumentary leishmaniasis patients are associated with the process of cure or aggravation of the disease, 41 patients were studied: 26 cases of cutaneous leishmaniasis (CL) and 15 of mucocutaneous leishmaniasis (MCL). During active disease the serum levels of TNF-alpha of MCL patients were significantly higher than those of CL patients and control subjects (healthy individuals and cutaneous lesions from other etiologies). The MCL patients had serum titers of TNF-alpha significantly lower at the end of antimonial therapy than before therapy. After a six-month follow-up, the MCL patients had serum levels of TNF-alpha similar to those observed at the end of the therapy as well as to those of Cl patients and control subjects. No significant variation in the serum levels of TNF-alpha was observed in CL patients throughout the study period (before, at the end of therapy and after a six-month follow-up). The possible relationship between the high TNF-alpha serum levels and severity of the disease is discussed.

Humans , Leishmaniasis, Cutaneous/drug therapy , Tumor Necrosis Factor-alpha