83 research outputs found

    An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART

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    HIV-associated Kaposi’s sarcoma (KS), which is caused by Kaposi’s sarcoma-associated herpesvirus, usually arises in the context of uncontrolled HIV replication and immunosuppression. However, disease occasionally occurs in individuals with durable HIV viral suppression and CD4 T cell recovery under antiretroviral therapy (ART). The underlying mechanisms associated with this phenomenon are unclear. Suppression of viral infections can be mediated by CD8 T cells, which detect infected cells via their T cell receptor and the CD8 coreceptor. However, CD8 T cells exhibit signs of functional exhaustion in untreated HIV infection that may not be fully reversed under ART. To investigate whether KS under ART was associated with phenotypic and functional perturbations of CD8 T cells, we performed a cross-sectional study comparing HIV-infected individuals with persistent KS under effective ART (HIV+ KS+) to HIV-infected individuals receiving effective ART with no documented history of KS (HIV+ KSneg). A subset of T cells with low cell surface expression of CD8 (“CD8dim T cells”) was expanded in HIV+ KS+ compared with HIV+ KSneg participants. Relative to CD8bright T cells, CD8dim T cells exhibited signs of senescence (CD57) and mitochondrial alterations (PGC-1α, MitoTracker) ex vivo. Mitochondrial activity (MitoTracker) was also reduced in proliferating CD8dim T cells. These findings indicate that an expanded CD8dim T cell population displaying features of senescence and mitochondrial dysfunction is associated with KS disease under ART. CD8 coreceptor down-modulation may be symptomatic of ongoing disease

    The burden of co-existing dermatological disorders and their tendency of being overlooked among patients admitted to muhimbili national hospital in Dar es Salaam, Tanzania

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    \ud Skin diseases are underestimated and overlooked by most clinicians despite being common in clinical practice. Many patients are hospitalized with co-existing dermatological conditions which may not be detected and managed by the attending physicians. The objective of this study was to determine the burden of co-existing and overlooked dermatological disorders among patients admitted to medical wards of Muhimbili National hospital in Dar es Salaam. A hospital-based descriptive cross-sectional study conducted at Muhimbili National hospital in Dar es Salaam, Tanzania. Patients were consecutively recruited from the medical wards. Detailed interview to obtain clinico-demographic characteristics was followed by a complete physical examination. Dermatological diagnoses were made mainly clinically. Appropriate confirmatory laboratory investigations were performed where necessary. Data was analyzed using the 'Statistical Package for Social Sciences' (SPSS) program version 10.0. A p-value of < 0.5 was statistically significant. Three hundred and ninety patients admitted to medical wards were enrolled into the study of whom, 221(56.7%) were females. The mean age was 36.7 ± 17.9 (range 7-84 years). Overall, 232/390 patients (59.5%) had co-existing dermatological disorders with 49% (191/390) having one, 9% (36/390) two and 5 patients (1%) three. A wide range of co-existing skin diseases was encountered, the most diverse being non-infectious conditions which together accounted for 36.4% (142/390) while infectious dermatoses accounted for 31.5% (123/390). The leading infectious skin diseases were superficial fungal infections accounting for 18%. Pruritic papular eruption of HIV/AIDS (PPE) and seborrheic eczema were the most common non-infectious conditions, each accounting for 4.3%. Of the 232/390 patients with dermatological disorders, 191/232 (82.3%) and 154/232 (66.3%) had been overlooked by their referring and admitting doctors respectively. Dermatological disorders are common among patients admitted to medical wards and many are not detected by their referring or admitting physicians. Basic dermatological education should be emphasized to improve knowledge and awareness among clinicians.\u

    The public health control of scabies: priorities for research and action.

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    Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary

    Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease

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    An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis
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