Background Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. Methods We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution, and compared with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by: IL-6 and IL-8 production in response to particulate challenge; phagocytosis of fluorescent-labelled beads and intraphagosomal oxidative burst capacity; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. Results We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte derived macrophages. Fine carbon black induced IL-8 release from monocyte derived and alveolar macrophages (p<0.05), with similar magnitude responses (log10 increases of 0.93 [SEM 0.2] vs 0.74 [SEM 0.19] respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (p=0.0015). There was no overall effect on killing of M. tuberculosis. Conclusion Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke exposed cells demonstrate reduced phagocytosis but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.
The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.
Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %-47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %-75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years.
By the beginning of July 2009 the West Midlands had seen more cases of novel H1N1 influenza (swine flu) than any other region in the U.K. Over a three-week period almost 850 people presented to Heartlands Hospital with flu-like symptoms. Of those admitted 52 adults were subsequently confirmed as having H1N1 infection. Most were younger than 30 and not from traditional influenza risk groups. The main risk factor for severe disease was asthma, and to a lesser extent pregnancy and obesity. Seven patients were admitted to intensive care and five developed an acute lung injury requiring prolonged admission. Two patients required extra corporeal membrane oxygenation and one died. Despite increased workload normal clinical services were unaffected. The hospital was not closed to admissions nor was it paralysed by staff absence. With a predicted second wave expected at the end of 2009, efforts to maintain effective community assessment remain crucial.
The immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART) in patients with advanced HIV. Because there is no confirmatory diagnostic test, the diagnosis is based on clinical presentation and exclusion of alternative causes for deterioration, such as antimicrobial drug resistance. Opportunistic infection treatment should be optimized. Mild cases may require symptomatic therapy alone or nonsteroidal anti-inflammatory drugs. Corticosteroids have been used to treat more severe cases of IRIS associated with mycobacterial and fungal infections. There is evidence from a randomized controlled trial that prednisone reduces morbidity and improves symptoms in paradoxical tuberculosis (TB)-IRIS. Neurological TB-IRIS is potentially life-threatening; high-dose corticosteroids are indicated and ART interruption should be considered if level of consciousness is depressed. When considering corticosteroid treatment clinicians should be aware of their side effects and only use them when the diagnosis of IRIS is certain. In viral forms of IRIS corticosteroids are generally avoided.
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