Clinical presentation of patients with seasonal influenza and pandemic influenza A (H1N1-2009) requiring hospitalisation.

Background. A sudden increase in the number of novel influenza A virus (pH1N1-2009) infection prompted us to compare the clinical presentation and outcomes of patients infected with pH1N1-2009 and seasonal influenza A virus during the postpandemic phase. Methods. During the period August 13 to September 27, 2010, case records of 106 patients with severe influenza like illness (ILI) and respiratory complications who underwent diagnostic testing by real-time polymerase chain reaction (RT-PCR) for confirmation of pH1N1-2009 were retrospectively studied. Results. Nineteen (17.9%) patients were tested positive for pH1N1-2009 and 78 (73.6%) were tested positive for seasonal influenza A virus. The mean age of patients infected with pH1N1-2009 was 45.2±15.3 years (range of 22 to 80 years). Common presenting symptoms included fever in 17 (89.4%), cough in 16 (84.2%), myalgia in 15 (78.9%) and breathlessness in 10 (52.6%) patients. The most common comorbidities included bronchial asthma/bronchitis/chronic obstructive pulmonary disease (COPD) in 4 (21%); followed by hypertension in 3 (15.8%) and diabetes in 3 (15.8%) patients. Overall, of the 97 influenza infected patients, 9 (9.3%) needed hospitalisation to the intensive care unit (ICU); one patient with COPD died due to multi-organ failure. Conclusions. Both the pandemic and seasonal strains were found to be co-circulating in the community. Patients with severe hypoxia, hypertension, acute respiratory distress syndrome and shock required ICU care.

Resolution of immune response by recombinant transforming growth factor-beta (rTGF-β) during influenza A virus infection.

Background & objectives: Replication of influenza A virus in the respiratory tract leads to cell damage and liberation of cytokines and chemokines. The in vivo cytokine induction and modulation by recombinant transforming growth factor- β1 (rTGF-β1) has not been studied. Therefore, in the present study the effect of rTGF-β1, a potent immunomodulatory cytokine which has anti-inflammatory properties and downregulates the release of inflammatory molecules, against influenza-virus infection in the airway of mice was investigated. Methods: rTGF-β1 was administered intravenously to mice with concomitant intranasal infection of influenza A/Udorn/317/72 (H3N2) virus, and the survival rate, virus titre, histopathological changes and levels of factors regulating inflammation in the airway fluid were analysed. Result: The immune response to influenza A virus was characterized by an influx of both macrophages and lymphocytes into the lungs of the infected host. rTGF-β1 significantly suppressed virus multiplication and improved the survival rate of mice. rTGF-β1 downregulated infiltration of neutrophils and the release of inflammatory molecules, such as interferon-gamma (IFN-γ), interleukin-1 β (IL-1β) and stimulated release of IL-10 that potentiates anti-inflammatory response into airway. Interpretation & conclusions: A generalized pulmonary inflammation does not contribute to viral clearance but represents an immunological background within which antiviral immunity operates. Treatment with rTGF-β1 reduced macrophage count and neutrophils influx in lungs of infected mice.

Influenza A (H1N1) 2009: a pandemic alarm.

At this critical juncture when the world has not yet recovered from the threat of avian infl uenza, the virus has returned in the disguise of swine infl uenza, a lesser known illness common in pigs. It has reached pandemic proportions in a short time span with health personnel still devising ways to identify the novel H1N1 virus and develop vaccines against it. The H1N1 virus has caused a considerable number of deaths within the short duration since its emergence. Presently, there are no effective methods to contain this newly emerged virus. Therefore, a proper and clear insight is urgently required to prevent an outbreak in the future and make preparations that may be planned well in advance. This review is an attempt to discuss the historical perspective of the swine fl u virus, its epidemiology and route of transmission to better understand the various control measures that may be taken to fi ght the danger of a global pandemic.

Infl uenza a virus induced apoptosis: Inhibition of DNA laddering & caspase-3 activity by zinc supplementation in cultured HeLa cells.

Background & objectives: The pathogenesis of infl uenza virus infection involves virus replication in epithelial cells of the respiratory tract and the consequent degeneration of infected cells. Infl uenza virus induces cellular degeneration following infection of cultured cells in vitro, and the cytopathic effect (CPE) occurs principally through apoptotic cell death. This study was undertaken to fi nd out the effect of zinc on infl uenza virus induced apoptosis in cultured HeLa cells. Methods: The sub-confl uent monolayer HeLa cells were used to study the effect of zinc on infl uenza virus induced apoptosis. The apoptotic markers viz., caspase-3 activity, phagocytic index, morphological changes, and DNA fragmentation were assayed. Results: When HeLa cells were infected with a cell adapted pathogenic strain of infl uenza A (A/Udorn/ 317/72H3N2) virus, DNA fragmentation was observed in virus infected cells by 24 h post infection and caspase-3 activity was maximum at 4 h post infection after which it reached to plateau. Treatment of cells with 0.1 5mM concentration of zinc till 8 h post infection inhibited DNA fragmentation and also caspase 3 activity was decreased signifi cantly up to 2 h post infection. Interpretation & conclusions: When the infected HeLa cells were incubated with adherent macrophages, effi cient phagocytosis occurred and the release of virus into the culture medium was inhibited. These results suggested that inhibitory effect on infl uenza virus induced apoptotic death of cultured cells can be determined at an early stage of the infection by treatment of zinc.

Time course of pulmonary pathology, cytokine influx and their correlation on augmentation of antigen challenge by influenza A virus infection.

A murine model of influenza A virus exacerbation of allergen induced airway inflammation, pulmonary histopathological changes, bronchoalveolar lavage fluid (BALF) analysis, cytokine influx and the time course of these events have been studied. The present study was undertaken to determine the relative contributions of Thl/Th2 cytokines to the histopathological changes in the lungs observed at 9, 12, 24 and 48 hr following antigen challenge in mice previously immunized with influenza A virus. BALF analysis of acute phase group revealed statistically significant increase in neutrophils at 9 hr, macrophages at 12 hr, lymphocytes and eosinophils at 24 hr, as compared to OVA-sensitized control mice. These changes were associated with an alteration in the levels of IL-4, IL-5 and IFN-gamma. A peak of IL-4 at 24 hr significantly enhanced bronchiolar and perivascular histopathology, whereas increased IL-5 level peaking at 24 hr was correlated with the enhanced infiltration of eosinophils in both BALF and lung tissue. There was simultaneous depletion of IL-10 an anti-inflammatory cytokine leading to persistence of pulmonary inflammation in case of acute phase group. Histopathology at 24 and 48 hr showed severe denudation of bronchiolar lining epithelium surrounded by dense chronic inflammatory infiltrate. Chronic interstitial infiltrate with focal loss of architecture, marked oedema, extravasation of RBCs from congested blood vessels and laying down of reticulin fibres was observed in acute phase. Thus, infection with influenza A virus on pre-existing asthmatic immunopathology elicits a cascade of Th2 cytokines with influx of inflammatory cells in BALF, mucosal and interstitial inflammation leading to asthma exacerbations.

Biological and epidemiological aspects of influenza virus H5N1 in context of India.

Since 1997, highly pathogenic avian influenza (HPAI) H5N1 virus crossed the species barriers from birds to humans and caused fatal disease, leading to great speculation about a possible influenza pandemic. This subtype is characterized by its pathogenicity in a large number of animal species and resistance to older class of antiviral drugs. At present, two out of three general conditions for the onset of pandemic have been met, emergence of new virus; and its ability to replicate in humans causing serious illness. Next influenza pandemic might be due to human to human transmission. This review addresses the biological and epidemiological aspects of influenza in context of India.

Defective interleukin-2 production and interleukin-2 receptor expression in pulmonary tuberculosis.

The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led to a complex relationship between it and its host, the human mononuclear phagocyte. The products of M. tuberculosis-specific T lymphocytes are essential for macrophage activation for intracellular mycobacterial killing. However, dysfunction cell-mediated immune response to infection with M. tuberculosis may contribute to progressive primary infection or reactivation of endogenous foci of mycobacteria. Th1 cells produce IL-2, which is essential for proper cellular immunity. The aim of this study was to identify the variation in IL-2 activity and soluble IL-2 receptor (IL-2 R) in peripheral blood lymphocyte in patients suffering with pulmonary tuberculosis. A significant decrease in IL-2 and IL-2 receptor level was observed in patients with pulmonary tuberculosis when compared to normal controls. Our results suggested that patients with pulmonary tuberculosis had a defect in IL-2 production. Better understanding of these interactions will allow the development of increasingly specific immune-based interventions for prevention and treatment of tuberculosis.

Role of Ca2+ in induction and secretion of dengue virus-induced cytokines.

The present study was undertaken to investigate the role of calcium ions (Ca2+) in the induction and secretion of the dengue type 2 virus induced cytotoxic factor and the cytotoxin. This was done by using calcium channel blocking drugs such as verapamil, nifedipine or diltiazem hydrochloride. The production of cytotoxic factor was significantly reduced by treatment of dengue type 2 virus infected mice with verapamil. Similarly, a dosedependent inhibition of the secretion of cytotoxic factor was observed, when spleen cells of the virus-primed mice were treated in vitro with the 3 calcium channel blockers. The production of cytotoxin by macrophages was abrogated by pretreatment with calcium channel blockers but had little effect on its secretion as shown by treatment of macrophages with verapamil at 1 h after the induction to later periods up to 18 h. The findings thus show that in the induction of both the cytokines Ca2+ plays a critical role; on the other hand it is required for the secretion of the cytotoxic factor but not for that of the cytotoxin.