Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults

BACKGROUND Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+) T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART. METHODS Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+) T-cell immunity. RESULTS We found lower naturally-acquired proliferative influenza-specific CD4(+) T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4(+) T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+) T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+) T-cells in peripheral blood. CONCLUSION Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations

Effect of Energy Density on the Consolidation Mechanism and Microstructural Evolution of Laser Cladded Functionally-Graded Composite Ti-Al System

The engagement of additive manufacturing (AM) technology in developing intermetallic coatings involves additional heat treatment with a view to obtaining desirable microstructure and mechanical properties. This eventually increases the lead time and the manufacturing cost. To address these challenges, this study explores the fabrication of gradient and laminar structures of titanium aluminide (Ti-Al) composite coatings deposited on Ti-6Al-4V substrate via a single step laser cladding (LC). The alterations in microstructural properties, chemical composition and phase analysis of the coatings reinforced with TiC were investigated as a function of laser energy density. Evaluation of the deposited samples reveals that FGM composite clads were fabricated from Ti-Al blended with TiC when LED was set at 17.50 J/mm2 . At the selected LED, a thermo-positive reaction between the constituents’ materials was induced and it resulted in the formation of intermetallic compounds (e.g. Ti2AlC, and 2 matrix phases) with a microhardness more than that of the substrate (Ti-6Al-4V alloy). This study provides new insights on the selection of process parameters for the coating manufacturers while employing low cost- and time-effective LC process for fabricating functional graded Ti-Al coatings.Mechanical Engineerin

Advanced Immune Suppression is Associated With Increased Prevalence of Mixed-Strain Mycobacterium tuberculosis Infections Among Persons at High Risk for Drug-Resistant Tuberculosis in Botswana

We examined factors associated with mixed-strain Mycobacterium tuberculosis infections among patients at high risk for drug-resistant tuberculosis in Botswana. Thirty-seven (10.0%) of 370 patients with tuberculosis had mixed M. tuberculosis infections, based on 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping. In log-binomial regression analysis, age <37 years (adjusted prevalence ratio [PR], 1.92; 95% confidence interval [CI], 1.01-3.57) and prior tuberculosis treatment (adjusted PR, 2.31; 95% CI, 1.09-4.89) were associated with mixed M. tuberculosis infections. Among human immunodeficiency virus-infected patients, prior tuberculosis treatment (adjusted PR, 2.11; 95% CI, 1.04-4.31) and CD4(+) T-cell count of <100 cells/μl (adjusted PR, 10.18; 95% CI, 2.48-41.71) were associated with mixed M. tuberculosis infections. Clinical suspicion of mixed M. tuberculosis infections should be high for patients with advanced immunosuppression and a prior history of tuberculosis treatment