HIV controllers are distinguished by chemokine expression profile and HIV-specific T-cell proliferative potential.

BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.

Serological survey of the novel influenza A H1N1 in inner city Winnipeg, Manitoba, 2009.

INTRODUCTION: Little is known about the determinants of pandemic H1N1 (pH1N1) infection in Canada among low-income, inner city populations. To inform future influenza planning, the seroprevalence of pH1N1 antibodies among inner city clinic attendees in Winnipeg (Manitoba) according to sociodemographic and risk factor characteristics were estimated and vaccination rates were explored. METHODS: Adults presenting to three inner city community clinics in Winnipeg from October 2009 to December 2009 were recruited as study participants (n=458). A questionnaire was administered to collect demographic, risk factor and symptom information, and a venous blood sample was collected for hemagglutination inhibition assay testing to detect the presence of antibodies against pH1N1. RESULTS: Approximately one-half (53%) of the study participants reported an annual household income of <$10,000/year, and 65% identified as Aboriginal. pH1N1 positivity was 5.7% among those enrolled early in the study and 15.5% among those enrolled later in the study. Positivity was higher among participants who were female, Aboriginal and in contact with children ≤5 years of age. The overall pH1N1 vaccination rate was 28%. DISCUSSION: pH1N1 positivity was high among low-income adults accessing clinics in Winnipeg's inner city compared with the general population. Of further concern were the low rates of uptake of both seasonal and pH1N1 influenza vaccinations. When planning for future influenza outbreaks, it is important to incorporate strategies for the prevention, control, and care of influenza among low-income and inner city adults.

INTRODUCTION: On ne sait pas grand-chose des déterminants de l'infection par la grippe pandémique H1N1 (pH1N1) dans les quartiers centraux du Canada. Pour étayer la future planification de la grippe, les chercheurs ont estimé la séroprévalence des anticorps du virus pH1N1 chez les personnes qui fréquentent une clinique des quartiers centraux de Winnipeg, au Manitoba, d'après les caractéristiques sociodémographiques et sur le plan des facteurs de risque, et ils ont examiné les taux de vaccination. MÉTHODOLOGIE: Les chercheurs ont recruté les adultes qui se sont présentés à trois cliniques communautaires des quartiers centraux de Winnipeg entre octobre et décembre 2009 à titre de participants à l'étude (n=458). Ils ont utilisé un questionnaire pour colliger de l'information sur la démographie, les facteurs de risque et les symptômes et prélevé un échantillon de sang veineux pour procéder à un test d'inhibition de l'hémagglutination afin de déceler la présence d'anticorps contre le virus pH1N1. RÉSULTATS: Environ la moitié (53 %) des participants à l'étude, dont 65 % étaient Autochtones, ont déclaré avoir un revenu familial annuel inférieur à 10 000 $. La positivité au virus pH1N1 était de 5,7 % chez les participants en début d'étude et de 15,5 % chez les personnes qui y ont participé plus tard. La positivité était plus élevée chez les participants de sexe féminin, autochtones ou en contact avec des enfants de cinq ans et moins. Le taux de vaccination global contre le virus pH1N1 s'élevait à 28 %. EXPOSÉ: La positivité au virus pH1N1 était élevée chez les adultes à faible revenu qui fréquentaient des cliniques des quartiers centraux de Winnipeg par rapport à la population générale. Par ailleurs, le faible taux de vaccination contre l'influenza saisonnière et contre la grippe pH1N1 était inquiétant. Dans le cadre de la planification de futures éclosions d'influenza, il sera important d'intégrer des stratégies de prévention, de contrôle et de soins de l'influenza chez les adultes à faible revenu des quartiers centraux.

Effectiveness of the pandemic H1N1 influenza vaccines against laboratory-confirmed H1N1 infections: population-based case-control study.

BACKGROUND: Excellent immune responses following 1 or 2 doses of the monovalent inactivated pandemic H1N1 vaccines have been documented, but the effectiveness of these vaccines against laboratory-confirmed H1N1 infections in the general population is not clear. We evaluated the effectiveness of the pandemic H1N1 and seasonal trivalent influenza vaccines (TIV) used during the 2009 mass vaccination campaign in Manitoba (Canada) in preventing laboratory-confirmed H1N1 infections. METHODS: A population-based case-control study using data from Cadham Provincial Laboratory (CPL) and the Manitoba Immunization Monitoring System (MIMS). All Manitoba residents ≥6 months of age who had a respiratory specimen tested at CPL for H1N1 were included in the study. Cases were individuals who tested positive for pandemic H1N1 influenza A by reverse transcriptase-PCR (N=1435). Controls were individuals who tested negative for both influenza A and B (N=2309). Information on receipt of TIV or H1N1 vaccine was obtained by record linkage with MIMS, the population-based province-wide immunization registry. RESULTS: Overall, the adjuvanted H1N1 vaccine was 86% (95%CI 75-93%) effective in preventing laboratory-confirmed H1N1 infections when vaccination occurred ≥14 days before testing. Effectiveness seemed lower among older (≥50 years) individuals [51% (-51 to 84%)] and among those with immunocompromising conditions [67% (-13 to 90%)]. There was also evidence that the H1N1 vaccine might be less effective among those who had received the 2009/10 TIV. DISCUSSION: The adjuvanted H1N1 vaccine used during Manitoba's H1N1 mass vaccination campaign was highly effective against laboratory-confirmed pandemic H1N1 infection, especially among children and younger adults.

Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic.

BACKGROUND: Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. METHODS: Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels. RESULTS: Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%-13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%-31.8%), as compared with 4.0% (95% CI 0.0%-11.9%) in Winnipeg and 8.9% (95% CI 0.0%-18.8%) in the rest of the province. INTERPRETATION: We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.

The role of regulatory T cells in chronic and acute viral infections.

Regulatory T cells, a subset of CD4(+) T lymphocytes, play a pivotal role in the maintenance of the balance between the tissue-damaging and protective effects of the immune response. These cells have immunosuppressive function and have been intensely studied in the context of autoimmunity, cancer, allergies, asthma, and infectious diseases. Their role in chronic and persistent viral infections is well appreciated. In acute viral infections, the function of these cells is still unclear. The host and pathogen factors that control the generation and activity of regulatory T cells and the role of these cells in modulating expansion, contraction, and development of immune memory in acute respiratory virus infection need to be further elucidated.

Hepatitis C virus infection among First Nation and non-First Nation people in Manitoba, Canada: a public health laboratory study.

Demographic information and laboratory test results on 136 169 clinical serum specimens submitted to the public health laboratory in Manitoba, Canada, for hepatitis C virus (HCV) testing between January 1995 and December 2003 were analyzed. The difference in the clearance rates of HCV infection, without therapeutic intervention, and the HCV genotypes infecting First Nation and non-First Nation people were studied. The rates of co-infection of HCV-positive individuals with other hepatitis viruses were also compared between the two study groups. The results of the analyses of the data indicated that there was a 4.4-fold increase in the number of specimens tested and a 4.9-fold decrease in HCV antibody (anti-HCV) positive cases during the study period. The proportion of specimens submitted for testing from First Nation individuals was lower than their proportion in the Manitoba population. Our study also indicated that there was a significantly higher proportion of First Nation patients who had self-limiting infection (patients cleared the infection and became HCV RNA negative without anti-HCV treatment) in comparison to non-First Nation patients. The proportion of First Nation females who had self-limiting infection was significantly higher than non-First Nation females. HCV genotype 1 infection represented more than 60% of HCV infection in Manitoba. The rate of individuals positive for the hepatitis A virus antibody in the HCV-positive population was higher among First Nation than non-First Nation individuals. On the other hand, there were more HCV-infected First Nation patients than non-First Nation patients who were not immune to the hepatitis B virus. The data indicate that fewer First Nation patients seek anti-HCV therapy in comparison to non-First Nation. In conclusion, the differences in the rates of HCV self-limiting infection between First Nation and non-First Nation individuals in Manitoba may reflect the genetic differences between the two cohorts, which may consequently affect the immune response to the HCV infection.

Parvovirus B19 associated adult Henoch Schönlein purpura.

BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated. METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies. CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells. CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.

Parvoviral infection of endothelial cells and its possible role in vasculitis and autoimmune diseases.

OBJECTIVE: To analyze a series of biopsies from 16 patients who, on the basis of clinical and dermatopathologic findings, had a spectrum of connective tissue diseases (CTD), autoinflammatory or CTD-like syndromes for parvoviral DNA, RNA, and protein. METHODS: Most of the patients were initially screened for parvoviral-related IgG and IgM antibodies. Parvoviral DNA was analyzed by solution phase polymerase chain reaction (PCR). In situ localization of viral VP1 RNA was accomplished by in situ reverse transcriptase (RT) PCR; viral protein (VP2) was detected by immunohistochemistry and these results correlated with the histologic findings. (J Rheumatol 2002;29:xxxx) RESULTS: Of 11 people tested, 10 had either IgG or IgM specific antibodies against parvovirus. Common histologic features of the 16 cases included an interface dermatitis, interstitial histiocytic infiltration with variable collagen necrobiosis, a mononuclear cell dominant vasculitis, and interstitial neutrophilia. Detection of parvoviral RNA by in situ RT-PCR in 14 of 16 cases corroborated solution phase PCR data and demonstrated that the endothelial cells and surrounding mononuclear cells were the viral target. Viral protein as revealed by immunohistochemisty showed an equivalent histologic distribution. Anti-tumor necrosis factor-alpha (TNF-alpha) therapy (etanercept) yielded dramatic improvement after worsening of symptoms with traditional immunosuppressive therapy in the 3 patients in whom this drug was administered; TNF-alpha mRNA was detected by in situ RT-PCR in the area of parvoviral infected cells. CONCLUSION: Parvoviral induced endothelialitis may be responsible for cases of "idiopathic" CTD.