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1.
Cytokine ; 149: 155747, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715475

RESUMO

Visceral leishmaniasis (VL) is caused by the protozoan Leishmania spp, transmitted by sand fly bites. VL is one of the deadliest tropical infection diseases, yet the coinfection with HIV virus drastically increases relapses, treatment failure and mortality. The concomitant action of these two pathogens leads to high cellular activation independently of the progression to AIDS. In addition, microbial translocation and bacterial infections are thought to contribute worsening the clinical picture. Identifying biomarkers associated with disease severity is of interest for clinical management of patients with VL-HIV/AIDS. Thus, we analyzed in the sera several markers including interleukins (IL-1ß, IL-6, IL-8, and IL-17), interferon-γ (IFN- γ), tumor necrosis factor (TNF), lipopolysaccharide (LPS), soluble CD14 (sCD14), macrophage migration inhibitory factor (MIF) and intestinal fatty acid-binding protein (IFABP). These markers were compared with disease severity in 24 patients with VL/HIV presenting different clinical outcomes. Disease severity was defined by the probability of death calculated using a score set system derived by the Kala-Cal® software. Probability of death ranged from 3.7% to 97.9%, with median of 28.8%. Five patients died (20%). At the univariate analysis, disease severity was correlated with TNF, IFN-γ and sCD14. LPS was positively correlated with sCD14 specifically in patients with low CD4+ count (CD4+ T-cell <200 cells/mL). Most importantly, the multivariate analysis including LPS, CD4+count and sCD14 showed that sCD14 was the only independent predictor for disease severity and death. Altogether, our results indicated that sCD14 is a powerful marker of pathogenicity and death for patients with VL-HIV/AIDS.


Assuntos
Biomarcadores/sangue , Coinfecção/sangue , Infecções por HIV/sangue , Leishmaniose Visceral/sangue , Adulto , Linfócitos T CD4-Positivos/metabolismo , Criança , Feminino , Humanos , Interferon gama/sangue , Interleucinas/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Índice de Gravidade de Doença
2.
BMC Infect Dis ; 21(1): 369, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33874901

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1ß), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4-5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. METHODS: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. RESULTS: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = - 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. CONCLUSIONS: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.


Assuntos
Anticorpos Antiprotozoários/sangue , Linfócitos T CD4-Positivos/citologia , Imunoglobulina G/sangue , Leishmania/imunologia , Leishmaniose Visceral/patologia , Adulto , Anfotericina B/uso terapêutico , Brasil , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Feminino , Infecções por HIV/complicações , Humanos , Interleucina-6/sangue , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva
3.
Neuroimmunomodulation ; 27(2): 113-122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756050

RESUMO

INTRODUCTION: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy associated with an inflammation of the central nervous system (CNS), being characterized by perivascular infiltration of inflammatory cells. HTLV-1-infected cells have the capacity to migrate through endothelial layers by enhancing adhesion receptor expression and corresponding ligands. T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cell migration and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. METHODS: Herein we studied the expression of 3 integrin alpha chains (CD49d, CD49e, and CD49f) on the membrane of T-cell subsets in patients infected by HTLV-1, both HAM/TSP patients and oligo/asymptomatic subjects who were asymptomatic or presented slight manifestations related to the virus infection. RESULTS: We observed higher peripheral blood frequency of CD49dhiCD4+ and CD49dhiCD8+ T cells in HTLV-1-infected patients. CONCLUSION: Our findings suggest that the increased expression of adhesion molecules, such as CD49d on T lymphocytes from HTLV-1-infected patients may contribute to the pathogenesis of the disease, in both oligo/asymptomatic and HAM/TSP-infected subjects. Accordingly, it is conceivable that there is a potential use of CD49d as target for a therapeutic approach aiming at blocking migration of activated T cells from HTLV-1-infected patients into the CNS, thus avoiding the progression to HAM/TSP.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Sistema Nervoso Central , Humanos , Inflamação , Subpopulações de Linfócitos T
4.
Sci Rep ; 14(1): 9870, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38684845

RESUMO

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum. Clinically, VL evolves with systemic impairment, immunosuppression and hyperactivation with hypergammaglobulinemia. Although renal involvement has been recognized, a dearth of understanding about the underlying mechanisms driving acute kidney injury (AKI) in VL remains. We aimed to evaluate the involvement of immunoglobulins (Igs) and immune complexes (CIC) in the occurrence of AKI in VL patients. Fourteen VL patients were evaluated between early treatment and 12 months post-treatment (mpt). Anti-Leishmania Igs, CIC, cystatin C, C3a and C5a were assessed and correlated with AKI markers. Interestingly, high levels of CIC were observed in VL patients up to 6 mpt. Concomitantly, twelve patients met the criteria for AKI, while high levels of cystatin C were observed up to 6 mpt. Plasmatic cystatin C was positively correlated with CIC and Igs. Moreover, C5a was correlated with cystatin C, CIC and Igs. We did not identify any correlation between amphotericin B use and kidney function markers in VL patients, although this association needs to be further explored in subsequent studies. Our data reinforce the presence of an important renal function impairment during VL, suggesting the involvement of Igs, CIC, and C5a in this clinical condition.


Assuntos
Injúria Renal Aguda , Complexo Antígeno-Anticorpo , Leishmaniose Visceral , Humanos , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/sangue , Injúria Renal Aguda/sangue , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/parasitologia , Masculino , Feminino , Complexo Antígeno-Anticorpo/sangue , Adulto , Biomarcadores/sangue , Pessoa de Meia-Idade , Cistatina C/sangue , Adolescente , Adulto Jovem , Anfotericina B/uso terapêutico , Leishmania infantum/imunologia
5.
Am J Trop Med Hyg ; 110(2): 228-233, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38109765

RESUMO

In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.


Assuntos
Infecções por HIV , Leishmania , Leishmaniose Mucocutânea , Humanos , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Contagem de Linfócito CD4 , Imunidade , Infecções por HIV/complicações
6.
Cytokine ; 61(1): 168-72, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23068083

RESUMO

American tegumentary leishmaniasis (ATL) is an infectious disease caused mostly by Leishmania(Viannia)braziliensis in Southeast Brazil. The clinical manifestations are vast, ranging from asymptomatic to severe mucosal leishmaniasis (ML). It has been suggested that variation of the pathogen does not fully explain the response spectrum and the variability of clinical manifestations. Previous data have shown that host genetics also play a role in disease outcome. Herein, we have tested the association of TNF, IL10, IL12 and MIF single nucleotide polymorphisms (SNPs) using a case-control study design including 110 cutaneous leishmaniasis (CL) patients and 682 healthy subjects. The genotype-phenotype correlation was also assessed using leishmania antigens to stimulate peripheral blood mononuclear cells obtained from cured CL patients. Results demonstrated that the MIF -173C allele is associated with leishmaniasis outcome and also with lower levels of MIF in culture supernatants. Also, the TNF -308AA genotype was statistically increased among leishmaniasis patients. The results showed here suggest that the lower levels of MIF produced by MIF -173C carriers could influence the host-Leishmania interaction, favoring infection and disease progression. On the other hand, high TNF levels can contribute to tissue damage, consequently leading to skin lesions.


Assuntos
Oxirredutases Intramoleculares/genética , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/genética , Leishmaniose Cutânea/imunologia , Fatores Inibidores da Migração de Macrófagos/genética , Adulto , Alelos , Estudos de Casos e Controles , Células Cultivadas , Feminino , Estudos de Associação Genética , Genótipo , Interações Hospedeiro-Patógeno/genética , Humanos , Interleucina-10/genética , Interleucina-12/genética , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética
7.
Mem Inst Oswaldo Cruz ; 107(8): 985-92, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23295747

RESUMO

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.


Assuntos
Anemia/parasitologia , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Ativação Linfocitária/imunologia , Malária Falciparum/imunologia , Parasitemia/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , Malária Falciparum/complicações , Masculino , Moçambique , Índice de Gravidade de Doença
8.
EClinicalMedicine ; 37: 100981, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34222847

RESUMO

BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

10.
Mem Inst Oswaldo Cruz ; 105(5): 692-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20835619

RESUMO

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%) and 34.8% of the patients were intravenous drug users (IVDU). Leishmaniasis was the first opportunistic infection in 60% of the HIV-1 patients. Fever occurred in all patients, although splenomegaly and hepatomegaly were absent in 21.7% of the cases. CD4+ T-cell counts were below 200 cells/mm(3) in 80% 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% 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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Doenças Endêmicas , Leishmaniose Visceral/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Brasil , Contagem de Linfócito CD4 , Feminino , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Fatores de Risco , Carga Viral , Adulto Jovem
11.
Front Immunol ; 11: 953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508833

RESUMO

Background: Visceral leishmaniasis/HIV-co-infected patients (VL/HIV) accounts for around 8% of VL reported cases in Brazil. Relapses of Leishmania infection after anti-leishmanial treatment constitute a great challenge in the clinical practice because of the disease severity and drug resistance. We have shown that non-relapsing-VL/HIV (NR-) evolved with increase of CD4+ T-cell counts and reduction of activated CD4+ and CD8+ T cells after anti-leishmanial treatment. This immune profile was not observed in relapsing-VL/HIV patients (R-), indicating a more severe immunological compromising degree. Elevated activation status may be related to a deficient immune reconstitution and could help to explain the frequent relapses in VL/HIV co-infection. Our aim was to evaluate if this gain of T cells was related to changes in the peripheral TCRVß repertoire and inflammatory status, as well as the possible thymus involvement in the replenishment of these newly formed T lymphocytes. Methods: VL/HIV patients, grouped into non-relapsing (NR- = 6) and relapsing (R- = 12) were evaluated from the active phase up to 12 months post-treatment (mpt). HIV-infected patients (non-VL) and healthy subjects (HS) were included. The TCRVß repertoire was evaluated ex vivo by flow cytometry, whereas the plasmatic cytokine levels were assessed by Luminex assay. To evaluate the thymic output, DNA was extracted from PBMCs for TCR rearrangement excision circles (TREC) quantification by qPCR. Results: VL/HIV cases presented an altered mobilization profile (expansions or retractions) of the TCRVß families when compared to HS independent of the follow-up phase (p < 0.05). TCRVß repertoire on CD4+ T-cells was more homogeneous in the NR-VL/HIV cases, but heterogeneous on CD8+ T-cells, since different Vß-families were mobilized. NR-VL/HIV had the inflammatory pattern reduced after 6 mpt. Importantly, VL/HIV patients showed number of TREC copies lower than controls during all follow-up. An increase of recent thymic emigrants was observed in NR-VL/HIV individuals at 10 mpt compared to R- patients (p < 0.01), who maintained lower TREC contents than the HIV controls. Conclusions: VL/HIV patients that maintain the thymic function, thus generating new T-cells, seem able to replenish the T lymphocyte compartment with effector cells, then enabling parasite control.


Assuntos
Coinfecção , Infecções por HIV/imunologia , Leishmaniose Visceral/imunologia , Ativação Linfocitária , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Relação CD4-CD8 , Estudos de Casos e Controles , Proliferação de Células , Citocinas/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/metabolismo , Leishmaniose Visceral/parasitologia , Fenótipo , Estudos Prospectivos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Recidiva , Subpopulações de Linfócitos T/parasitologia , Subpopulações de Linfócitos T/virologia , Timo/parasitologia , Timo/virologia , Fatores de Tempo , Resultado do Tratamento
12.
Pathogens ; 9(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861618

RESUMO

Giardiasis is an intestinal infection caused by ingestion of water or food contaminated with cysts of Giardia lamblia. Susceptibility is higher in children and overall prevalence can reach up to 90% in low-income areas, although outbreaks are also reported in developed countries. Both parasite and immune-mediated epithelial damage has been observed in vitro and in animal models. However, whether enterocytes are directly damaged during infection is not entirely known. Our goal was to identify whether plasma levels of intestinal fatty acid binding protein (I-FABP), a marker of enterocyte damage, are related to the immune response in giardiasis. Blood plasma was collected from 31 children (19 Giardia-positive) from a public day care in Rio de Janeiro, Brazil. The levels of I-FABP were increased in Giardia-infected children compared to children without detectable infection. There was no difference in I-FABP levels in giardiasis caused by different genetic assemblages of Giardia. Levels of IL-8 were decreased, while there was a trend to elevated IL-17 in the Giardia-positive children. A positive correlation was observed between I-FABP and IL-17 levels as well as TNF, suggesting that epithelial damage can be related to cytokine production during giardiasis. These results help elucidate the relationship between the disruption of the intestinal mucosal barrier and immune responses to G. lamblia in children.

13.
PLoS Negl Trop Dis ; 8(9): e3136, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25233461

RESUMO

Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Leishmaniose Visceral/epidemiologia , Brasil/epidemiologia , Coinfecção/parasitologia , Coinfecção/virologia , Infecções por HIV/parasitologia , Humanos , América Latina/epidemiologia , Leishmaniose Visceral/virologia
14.
Int J Microbiol ; 2012: 364534, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22956960

RESUMO

Visceral Leishmaniasis (VL) is an infectious disease which constitutes a serious public health problem, integrating the list of neglected tropical diseases. The disease is characterized by a Leishmania-specific immune suppression T-cell depletion and a decrease of other hematopoietic cells. In parallel, an immunostimulatory response also occurs, represented by polyclonal B lymphocytes, T-cell activation, and systemic proinflammatory responses. Parasite antigens were believed to mediate both suppression and activation mechanisms, but these concepts are constantly being revised. Similar to reports on HIV/AIDS, we have proposed that gut parasitation by amastigotes and lymphocyte depletion could also affect gut-associated lymphoid tissue, leading to mucosal barrier breach and predisposing to microbial translocation. An increment of plasmatic lipopolysaccharide (LPS) levels observed in Brazilian VL patients was implicated in the reduced blood CD4(+) and CD8(+) T cell counts, systemic T-cell activation, pro-inflammatory cytokines and MIF plasma levels, suggesting that a bacterial molecule not associated with Leishmania infection can exert deleterious effects on immune system. Recent results also pointed that the proinflammatory response was potentiated in VL/HIV-AIDS coinfected patients. The LPS-mediated cell activation adds another concept to the immunopathogenesis of VL and can bring a rational for new therapeutic interventions that could ameliorate the management of these patients.

15.
PLoS One ; 6(12): e28735, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22205964

RESUMO

BACKGROUND: It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. METHODS/PRINCIPAL FINDINGS: Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. CONCLUSION/SIGNIFICANCE: These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/imunologia , Hanseníase/complicações , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/induzido quimicamente , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Síndrome Inflamatória da Reconstituição Imune/terapia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Mem. Inst. Oswaldo Cruz ; 107(8): 985-992, Dec. 2012. graf
Artigo em Inglês | LILACS | ID: lil-660644

RESUMO

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.


Assuntos
Adulto , Feminino , Humanos , Masculino , Anemia/parasitologia , /imunologia , Infecções por HIV/imunologia , Ativação Linfocitária/imunologia , Malária Falciparum/imunologia , Parasitemia/imunologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , Estudos de Casos e Controles , Estudos Transversais , Infecções por HIV/complicações , Moçambique , Malária Falciparum/complicações , Índice de Gravidade de Doença
18.
Mem. Inst. Oswaldo Cruz ; 105(5): 692-697, Aug. 2010. graf, tab
Artigo em Inglês | LILACS | ID: lil-557232

RESUMO

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.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Infecções Oportunistas Relacionadas com a AIDS , Doenças Endêmicas , Leishmaniose Visceral , Infecções Oportunistas Relacionadas com a AIDS , Infecções Oportunistas Relacionadas com a AIDS , Anfotericina B , Antiprotozoários , Brasil , Leishmaniose Visceral , Leishmaniose Visceral , Meglumina , Compostos Organometálicos , Fatores de Risco , Carga Viral
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