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1.
PLoS Negl Trop Dis ; 15(11): e0009887, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34748560

RESUMO

BACKGROUND: Brazil remains endemic for infection by the human immunodeficiency virus (HIV) and leprosy, having a major impact on public health and the life quality of affected patients. Although the relevance of this co-infection is recognized, several aspects, such as the immune response, are not yet fully understood. The objective of this study was to investigate the expression of FOXP3+ Treg cells in leprosy skin lesions and to correlate their clinical forms, laboratory characteristics (CD4, CD8, and CV), and the immune reconstitution syndrome in HIV-leprosy co-infection. METHODOLOGY/PRINCIPAL FINDINGS: An observational, cross-sectional, and analytical study was carried out comparing four groups of patients: those with concomitant diagnosis of leprosy and HIV infection without a leprosy reaction, those with leprosy and HIV co-infection patients with a reverse reaction (RR), those with leprosy without HIV and without reaction, and those with leprosywithout HIV and with RR. The patients were diagnosed at a dermatology outpatient clinic located in Belém, Pará, Brazil, from 2003 to 2017. In the sample studied, there was a positive correlation between FOXP3+ cell density and viral load, negative correlation with blood CD4+ (not statistically significant), significant positive correlation in CD8 count in patients with leprosy reaction, and positive relationship in patients with IRIS. The density of cells expressing FOXP3 was higher in the BL/LL forms in patients without HIV, although the difference was not statistically significant. However, the cell mean was higher in the TT/BT forms in patients co-infected with leprosy and HIV, showing contradictory results. CONCLUSIONS/SIGNIFICANCE: These findings support that higher activity of the HIV may stimulate or result in a higher expression of FOXP3-Tregs and that they may be involved in active immunosuppression observed at the infection site at the tissue level. This supports the need to expand studies on FOXP3+ Treg cells in co-infected patients.


Assuntos
Coinfecção/genética , Fatores de Transcrição Forkhead/genética , Infecções por HIV/genética , Hanseníase/genética , Adolescente , Adulto , Idoso , Brasil , Linfócitos T CD8-Positivos/imunologia , Criança , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/virologia , Estudos Transversais , Feminino , Fatores de Transcrição Forkhead/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Hanseníase/imunologia , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/fisiologia , Carga Viral , Adulto Jovem
2.
PLoS Negl Trop Dis ; 13(5): e0006967, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31042700

RESUMO

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). METHODS: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). RESULTS: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.


Assuntos
Portador Sadio/virologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Paraparesia Espástica Tropical/diagnóstico , Provírus/fisiologia , Carga Viral , Adulto , Idoso , Doenças Assintomáticas , Brasil , Estudos de Coortes , Feminino , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/virologia , Provírus/genética
3.
J Med Virol ; 91(5): 775-780, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30512182

RESUMO

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.


Assuntos
Hepatite B/epidemiologia , Hanseníase/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Estudos Transversais , DNA Viral/sangue , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto Jovem
7.
J Cutan Med Surg ; 12(3): 126-32, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18544296

RESUMO

BACKGROUND: Dermatologic conditions are often an early clue to human immunodeficiency virus (HIV) infection. As the disease progresses and the host immunity fails, patients may develop a number of skin conditions. At this point, they have a dominant T helper 2 immunologic response. After the initiation of antiretroviral therapy, the T helper 1 response is restored, and some skin problems, paradoxically, make their appearance then. CONCLUSION: Herpes zoster, mucocutaneous herpes, eosinophilic folliculitis, and mycobacterial infections have been known to occur at this stage. This may be because immune restoration of a host's immunity causes recognition of silent or latent infection and results in development of the condition. We report five cases that were seen at our center during a 2-year period.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções por HIV/imunologia , Dermatopatias/imunologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Animais , Contagem de Linfócito CD4 , Diagnóstico Diferencial , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/imunologia , Humanos , Índia , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/imunologia , Masculino , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/imunologia , Prognóstico , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Síndrome , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/imunologia , Carga Viral
8.
Tuberculosis (Edinb) ; 88(5): 453-61, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18495539

RESUMO

A prospective and multi-centre study has allowed us to analyse antibody responses and Mycobacterium tuberculosis clinical isolate genotypes on 24 consecutive HIV-TB co-infected patients treated with Highly Active Antiretroviral Therapy (HAART) who either went on to develop a TB Immune Restoration Syndrome (TB-IRS), or not. Circulating free and immune-complexed antibodies against ManLAM, ESAT-6/CFP10 and PGL-Tb1 in HIV-TB co-infected patients were measured by ELISA at the initiation of anti-TB treatment, at the date of HAART initiation and thereafter. Presence of circulating B cells was also monitored by in vitro antibody production (IVAP) against ESAT-6/CFP10 and PGL-Tb1. Finally, 16 out of 24M. tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing. Eleven patients (45.8%) experienced TB-IRS (TB-IRS+). Significantly, lower anti-PGL-Tb1 antibody levels were identified in TB-IRS+ compared to TB-IRS-negative patients prior to TB-IRS development. These very low levels were neither related to CD4 counts nor with complexed antibodies. No difference in antibody levels was observed with the other tested antigens. In addition, no specific strain genotype was associated with TB-IRS. The presence of specific anti-PGL-Tb1 antibodies only in TB-IRS-negative patients represents for the first time an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB co-infected patients starting HAART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Antígenos de Bactérias/biossíntese , Glicolipídeos/biossíntese , Síndrome Inflamatória da Reconstituição Imune/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Carga Viral
9.
Immunology ; 124(2): 206-14, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18284466

RESUMO

Leprosy and human immunodeficiency virus-1 (HIV-1) are examples of human infections where interactions between the pathogen and the host cellular immunity determine the clinical manifestations of disease. Hence, a significant immunopathological interaction between HIV-1 and leprosy might be expected. In the present study we explored several aspects of cellular immunity in patients co-infected with HIV-1 and Mycobacterium leprae. Twenty-eight individuals were studied, comprising four groups: healthy controls, HIV-1 and M. leprae co-infection, HIV-1 mono-infection, and M. leprae mono-infection. Subjects in the mono-infection and co-infection groups were matched as far as possible for bacillary load and HIV disease status, as appropriate. Peripheral blood mononuclear cells (PBMC) were analysed using six- and seven-colour flow cytometry to evaluate T-cell subpopulations and their activation status, dendritic cell (DC) distribution phenotypes and expression of IL-4 by T cells. The co-infected group exhibited lower CD4 : CD8 ratios, higher levels of CD8(+) T-cell activation, increased V delta : V delta 2 T cell ratios and decreased percentages of plasmacytoid DC, compared with HIV-1 mono-infected subjects. Across infected groups, IL-4 production by CD4(+) T lymphocytes was positively correlated with the percentage of effector memory CD4(+) T cells, suggesting antigenically driven differentiation of this population of T cells in both HIV-1 and M. leprae infections. Co-infection with M. leprae may exacerbate the immunopathology of HIV-1 disease. A T helper 2 (Th2) bias in the CD4(+) T-cell response was evident in both HIV-1 infection and leprosy, but no additive effect was apparent in co-infected patients.


Assuntos
Infecções por HIV/complicações , HIV-1 , Hanseníase/complicações , Adulto , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Feminino , Infecções por HIV/imunologia , HIV-1/isolamento & purificação , Humanos , Imunidade Celular , Interleucina-4/biossíntese , Hanseníase/imunologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Subpopulações de Linfócitos T/imunologia , Carga Viral
11.
Lepr Rev ; 76(2): 162-6, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16038250

RESUMO

In a retrospective study, five patients are reported who suffered from a Mycobacterium leprae/HIV co-infection and were treated for their HIV infection with HAART. In four patients, this revealed their leprosy and induced a type I leprosy reaction. Two patients who were lepromin negative at diagnosis were retested after about 1 year of anti-retroviral treatment, and found to be positive.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Terapia Antirretroviral de Alta Atividade , Hansenostáticos/uso terapêutico , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Brasil/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral
12.
Artigo em Inglês | MEDLINE | ID: mdl-16394440

RESUMO

The differential diagnosis of oral ulcerations in a patient with AIDS/HIV infection is often challenging to the clinician. While old diseases have appeared in a new garb, many new ones are also being recognized. The association of Behetaet's disease and AIDS/HIV infection has been recently recognized. We present an HIV-positive patient having oro-genital aphthosis conforming to the diagnostic criteria for Behetaet's disease. Erythema nodosum, periphlebitis, erythematous papulopustular lesions, half and half nails, ocular congestion, raised ESR and dimorphic anemia were some other features present. He had low CD4+/CD8+ counts. He had no other HIV-related disease. He responded well to triple anti-retroviral treatment alone. The possible pathomechanism of the occurrence of both diseases is also discussed.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Síndrome de Behçet/diagnóstico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Adulto , Síndrome de Behçet/complicações , Contagem de Linfócito CD4 , Seguimentos , Infecções por HIV/complicações , Humanos , Índia , Masculino , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Carga Viral
13.
J Virol ; 78(21): 11506-18, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15479792

RESUMO

A unique opportunity for the study of the role of serial passage and cross-species transmission was offered by a series of experiments carried out at the Tulane National Primate Research Center in 1990. To develop an animal model for leprosy, three black mangabeys (BkMs) (Lophocebus aterrimus) were inoculated with lepromatous tissue that had been serially passaged in four sooty mangabeys (SMs) (Cercocebus atys). All three BkMs became infected with simian immunodeficiency virus from SMs (SIVsm) by day 30 postinoculation (p.i.) with lepromatous tissue. One (BkMG140) died 2 years p.i. from causes unrelated to SIV, one (BkMG139) survived for 10 years, whereas the third (BkMG138) was euthanized with AIDS after 5 years. Histopathology revealed a high number of giant cells in tissues from BkMG138, but no SIV-related lesions were found in the remaining two BkMs. Four-color immunofluorescence revealed high levels of SIVsm associated with both giant cells and T lymphocytes in BkMG138 and no detectable SIV in the remaining two. Serum viral load (VL) showed a significant increase (>1 log) during the late stage of the disease in BkMG138, as opposed to a continuous decline in VL in the remaining two BkMs. With the progression to AIDS, neopterin levels increased in BkMG138. This study took on new significance when phylogenetic analysis unexpectedly showed that all four serially inoculated SMs were infected with different SIVsm lineages prior to the beginning of the experiment. Furthermore, the strain infecting the BkMs originated from the last SM in the series. Therefore, the virus infecting BkMs has not been serially passaged. In conclusion, we present the first compelling evidence that direct cross-species transmission of SIV may induce AIDS in heterologous African nonhuman primate (NHP) species. The results showed that cross-species-transmitted SIVsm was well controlled in two of three BkMs for 2 and 10 years, respectively. Finally, this case of AIDS in an African monkey suggests that the dogma of SIV nonpathogenicity in African NHP hosts should be reconsidered.


Assuntos
Cercocebus atys/virologia , Cercocebus/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Animais , Anticorpos Antivirais/sangue , Contagem de Linfócito CD4 , Imuno-Histoquímica , Neopterina/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/imunologia , Vírus da Imunodeficiência Símia/patogenicidade , Carga Viral
14.
J Med Primatol ; 29(3-4): 259-67, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11085588

RESUMO

Groups of rhesus monkeys were inoculated with: 1) simian immunodeficiency virus (SIV)B670 alone; 2) Mycobacterium leprae alone; 3) SIV plus M. leprae on the same day; and 4) M. leprae 2 weeks after SIV. Animals were monitored at intervals for virus loads, antibody responses to M. leprae glycolipid antigens and to SIV Gp120, T-cell CD4+ and CD4+ CD29+ subset percentages, leprosy and acquired immunodeficiency syndrome (AIDS) clinical symptoms. Five out of six animals developed leprosy in each co-inoculated group, compared to one out of six in the M. leprae-only-inoculated group, indicating that M. leprae/SIV co-infection increases the susceptibility to leprosy, regardless of the timing of the two infections. Animals in the co-infected group that received M. leprae 2 weeks after SIV had a significantly slower rate of AIDS progression and long-term survival was significantly greater (three out of six) compared to the group inoculated with SIV alone (zero out of seven). All M. leprae-only-inoculated animals (six out of six) survived. Post-SIV-inoculation, a rapid decrease in the percentages of CD4 + and CD4 + CD29 + T-cells was observed in the SIV-only-inoculated group that was significantly blocked by co-inoculation with M. leprae 2 weeks after SIV, but not by SIV on the same day. The virus load set point was increased by approximately two logs in the group inoculated with M. leprae and SIV on the same day compared to SIV 2 weeks prior to M. leprae or the SIV-only-inoculated group. The results indicate that M. leprae, inoculated 2 weeks after SIV, decreased the pathogenicity of SIV compared to inoculation of M. leprae and SIV on the same day or SIV alone. The decreased pathogenicity correlated with a diminished loss of CD4 + and CD4 + CD29 + T-cell subsets in the group inoculated with M. leprae 2 weeks after SIV compared to the group inoculated with SIV alone. IgG antibody responses to M. leprae-specific cell wall phenolic glycolipid-I antigen were inhibited by 2-week-prior or same-day SIV co-inoculation compared to M. leprae-only inoculated animals. The IgG anti-lipoarabinomannan antibody response was enhanced in the group inoculated with M. leprae and SIV on the same day compared to the groups inoculated with M. leprae alone or SIV 2 weeks prior to M. leprae. Antibody responses to SIV Gp120 antigen were unimpaired in both co-inoculated groups compared to SIV-only-inoculated groups. The antibody results show that the immune responses to SIV and M. leprae are interrelated in SIV/M. leprae co-infected animals.


Assuntos
Hanseníase/fisiopatologia , Glicoproteínas de Membrana , Mycobacterium leprae , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Vírus da Imunodeficiência Símia , Proteínas do Envelope Viral , Animais , Anticorpos Antivirais/sangue , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Progressão da Doença , Proteína gp120 do Envelope de HIV/imunologia , Imunoglobulina G/sangue , Hanseníase/complicações , Hanseníase/imunologia , Macaca mulatta , Mycobacterium leprae/isolamento & purificação , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Taxa de Sobrevida , Subpopulações de Linfócitos T/imunologia , Carga Viral
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