Infecciologia
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- TiflitePublication . Monteiro, JA; Martins, TV; Morgado, ATiflite, síndrome fleo-cecal e enterocolite neutropénica serão denominações diversas do que parece ser uma infecção localizada à mucosa cecal, provocada por Clostridia. Habitualmente descrita em doentes neutropénicos, com leucémias ou após terapêutica anti-neoplásica, também tem sido descrita em doentes infectados por vírus da imunodeficiência humana, como no caso que apresentamos. O seu diagnóstico nem sempre é claro, tornando-se ainda mais problemático em doentes imunodeprimidos, nos quais múltiplas situações e podem apresentar com sintomas semelhantes. Todavia a um diagnóstico precoce deve seguir-se uma terapêutica médica agressiva, e se nalguns casos uma intervenção cirúrgica se sorna imperiosa, noutros poderá ser desnecessária. O seu controle a médio e a longo prazo poderá ser particularmente difícil.
- Investigation and Control of a Large Outbreak of Multi-Drug Resistant Tuberculosis at a Central Lisbon HospitalPublication . Hannan, MM; Peres, H; Maltez, F; Hayward, AC; Machado, J; Morgado, A; Proença, R; Nelson, MR; Bico, J; Young, DB; Gazzard, BSAn increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.
- Moluscos Contagiosos Exuberantes em Síndrome de Reconstituição ImunológicaPublication . Pereira, B; Fernandes, C; Nachiambo, E; Catarino, MC; Rodrigues, A; Cardoso, JO Síndrome de Reconstituição Imunológica (SRI) é uma entidade descrita recentemente na qual doentes seropositivos para o VIH com imunodepressão grave e após iniciarem Terapêutica Antiretroviral (TAR), desenvolvem reacções inflamatórias associadas a diferentes agentes patogénicos. Foram já reportados casos de SRI associados a vários agentes infecciosos como M. Avium Complex, Mycobacterium Tuberculosis e Pneumocystis jirovecci. As manifestações cutâneas no SRI são comuns tendo já sido descritos casos de Herpes Zoster, Doença de Hansen, Sarcoma de Kaposi, Sarcoidose e Granulomas de corpo estranho. Descreve-se o caso de um doente com numerosos e exuberantes Moluscos Contagiosos na face, pescoço e área genital que surgiram pouco tempo após o início da TAR coincidindo com o aumento na contagem de CD4 e diminuição da carga viral. Com a progressão da reconstituição imunológica as lesões resolveram espontaneamente. Presume-se que os Moluscos Contagiosos sejam lesões comuns no contexto do SRI mas pouco reportadas. Apresentamos este caso pela sua exuberância clínica e relação bem documentada com a reconstituição imunológica chamando, portanto, a atenção para esta manifestação do SRI.
- The Role of the Humoral Immune Response in the Molecular Evolution of the Envelope C2, V3 and C3 Regions in Chronically HIV-2 Infected PatientsPublication . Borrego, P; Marcelino, JM; Rocha, C; Doroana, M; Antunes, F; Maltez, F; Gomes, P; Novo, C; Barroso, H; Taveira, NBACKGROUND: This study was designed to investigate, for the first time, the short-term molecular evolution of the HIV-2 C2, V3 and C3 envelope regions and its association with the immune response. Clonal sequences of the env C2V3C3 region were obtained from a cohort of eighteen HIV-2 chronically infected patients followed prospectively during 2-4 years. Genetic diversity, divergence, positive selection and glycosylation in the C2V3C3 region were analysed as a function of the number of CD4+ T cells and the anti-C2V3C3 IgG and IgA antibody reactivity RESULTS: The mean intra-host nucleotide diversity was 2.1% (SD, 1.1%), increasing along the course of infection in most patients. Diversity at the amino acid level was significantly lower for the V3 region and higher for the C2 region. The average divergence rate was 0.014 substitutions/site/year, which is similar to that reported in chronic HIV-1 infection. The number and position of positively selected sites was highly variable, except for codons 267 and 270 in C2 that were under strong and persistent positive selection in most patients. N-glycosylation sites located in C2 and V3 were conserved in all patients along the course of infection. Intra-host variation of C2V3C3-specific IgG response over time was inversely associated with the variation in nucleotide and amino acid diversity of the C2V3C3 region. Variation of the C2V3C3-specific IgA response was inversely associated with variation in the number of N-glycosylation sites. CONCLUSION: The evolutionary dynamics of HIV-2 envelope during chronic aviremic infection is similar to HIV-1 implying that the virus should be actively replicating in cellular compartments. Convergent evolution of N-glycosylation in C2 and V3, and the limited diversification of V3, indicates that there are important functional constraints to the potential diversity of the HIV-2 envelope. C2V3C3-specific IgG antibodies are effective at reducing viral population size limiting the number of virus escape mutants. The C3 region seems to be a target for IgA antibodies and increasing N-linked glycosylation may prevent HIV-2 envelope recognition by these antibodies. Our results provide new insights into the biology of HIV-2 and its relation with the human host and may have important implications for vaccine design.
- Severe Proctitis Due to Lymphogranuloma Venereum (Chlamydia Trachomatis)Publication . Coelho, R; Fernandes, C; Machado, J; Correia, F; Martins, T; Maltez, F; Cardoso, J
- Leprosy and Kaposi Sarcoma Presenting as an Immune Reconstitution Inflammatory Syndrome in a Patient with AIDSPublication . Medeiros, S; Coelho, R; Fernandes, C; Catarino, MC; Afonso, A; Vieira, R; Rodrigues, A; Cardoso, JThe simultaneous presence of infectious organisms within cutaneous lesions of Kaposi sarcoma in persons with AIDS has been demonstrated. We describe a patient with concurrent leprosy and Kaposi sarcoma presenting as an immune reconstitution inflammatory syndrome in the setting of AIDS.
- Hansen's Disease in an HIV Patient Complicated by Deep Vein Thrombosis: a Rare Complication of Thalidomide TherapyPublication . Medeiros, S; Fernandes, C; Martins, N; Machado, J; Kutzner, H; Afonso, A; Vieira, R; Maltez, F; Cardoso, J
- Atypical Case of Mediterranean Spotted FeverPublication . Figueira-Coelho, J; Martins, T; Machado, J; Maltez, FThe authors present a case of atypical severe (malignant) Mediterranean spotted fever, with a brief review on the subject. Although not previously described in Brazil, the possibility of imported cases, especially from Portuguese tourists, is real. This case report highlights the severe form of the disease and the possibility of atypical presentation with confounding differential diagnosis. A brief review of classical presentation is also done. The authors believe it is a valid paper and a good contribution to your Journal of Infectious Diseases. The content of the manuscript represents the views of the coauthors, and neither the corresponding author nor the coauthors have submitted duplicate or overlapping manuscripts elsewhere.
- Coreceptor Usage by HIV-1 and HIV-2 Primary Isolates: The Relevance of CCR8 Chemokine Receptor as an Alternative CoreceptorPublication . Calado, M; Matoso, P; Santos-Costa, Q; Espirito-Santo, M; Machado, J; Rosado, L; Antunes, K; Mansinho, K; Lopes, MM; Maltez, F; Santos-Ferreira, MO; Azevedo-Pereira, JMThe human immunodeficiency virus replication cycle begins by sequential interactions between viral envelope glycoproteins with CD4 molecule and a member of the seven-transmembrane, G-protein-coupled, receptors' family (coreceptor). In this report we focused on the contribution of CCR8 as alternative coreceptor for HIV-1 and HIV-2 isolates. We found that this coreceptor was efficiently used not only by HIV-2 but particularly by HIV-1 isolates. We demonstrate that CXCR4 usage, either alone or together with CCR5 and/or CCR8, was more frequently observed in HIV-1 than in HIV-2 isolates. Directly related to this is the finding that the non-usage of CXCR4 is significantly more common in HIV-2 isolates; both features could be associated with the slower disease progression generally observed in HIV-2 infected patients. The ability of some viral isolates to use alternative coreceptors besides CCR5 and CXCR4 could further impact on the efficacy of entry inhibitor therapy and possibly also in HIV pathogenesis.
- Baseline Susceptibility of Primary HIV-2 to Entry InhibitorsPublication . Borrego, P; Calado, R; Marcelino, JM; Bártolo, I; Rocha, C; Cavaco-Silva, P; Doroana, M; Antunes, F; Maltez, F; Caixas, U; Barroso, H; Taveira, NBACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T-cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.