Magdy Dawood

Helicobacter pylori in the Canadian arctic : Seroprevalence and detection in community water samples

OBJECTIVES:Many North American arctic communities are characterized by risk markers associated with Helicobacter pylori (H. pylori) infection, including overcrowded housing and inadequate water supply and sanitation systems. Our aim was to determine the seroprevalence of H. pylori infection in two traditional Inuit communities in the central Canadian arctic and to test for the presence of H. pylori, by polymerase chain reaction (PCR), in local water supplies.METHODS:Samples of venous whole blood from adults and capillary blood from children were collected and analyzed by enzyme immunoassay and Helisal Rapid Test, respectively, for IgG antibody to H. pylori. Antibodies to CagA were detected by enzyme immunoassay, and ABO and Lewis antigens were also determined. Demographic and clinical information were collected by questionnaire. Water samples from each community were tested for H. pylori by PCR.RESULTS:One hundred-thirty (50.8%) of 256 subjects from the two communities were positive for H. pylori IgG antibodies. Seropositive subjects were more likely to be male, compared with seronegative individuals (p= 0.01). Antibody status did not differ with respect to age, community, alcohol or cigarette use, number of persons per household, gastrointestinal complaints or previous investigations, medications, or presence of blood group O, Lewis a−b+. CagA antibodies were detected in 78 (61.9%) of 126 H. pylori-seropositive subjects tested; however, 41 (35.3%) of 116 H. pylori-seronegative subjects were also CagA positive. Water samples taken from the water delivery truck in Chesterfield Inlet and two lakes near Repulse Bay were positive for H. pylori.CONCLUSION:The seroprevalence of H. pylori in the study group was higher than rates in southern Canadian populations, but lower than the seroprevalence previously documented in a Canadian subarctic Indian (First Nations) community. The detection of H. pylori in local water supplies may indicate a natural reservoir for the organism or possible contamination from human sewage.

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.

Parvovirus B19 associated adult Henoch Schönlein purpura

Background:  Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegeners 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.

Seroprevalence of Helicobacter pylori, Incidence of Gastric Cancer, and Peptic Ulcer-Associated Hospitalizations in a Canadian Indian Population

The living conditions of many aboriginalcommunities in Canada may place their residents at riskfor H. pylori infection. Our aims were to determine: (1)the seroprevalence of H. pylori in a traditional Indian community, (2) the clinical relevance ofH. pylori infection in this population, and (3) if H.pylori could be identified by polymerase chain reactionfrom the local water. A demographic questionnaire was administered, and blood was collected fromsubjects in an Indian community in northwesternManitoba. The serum was analyzed by ELISA for IgG to H.pylori and to CagA. ABO and Lewis antigens were tested. Age-adjusted incidence of gastric cancer and ofhospitalizations associated with diagnoses of pepticulcer were determined for the Indian and non-IndianManitoba population in the years 1989-1993. Nested PCR was performed on lake water using H.pylori-specific primers and the amplicons probed with aninternal Dig-labeled probe. Three hundred six (59%) ofapproximately 518 individuals who were resident in the community at the time of the study wereenrolled. The ELISA for H. pylori was positive in 291(95%). There was no association between H. pyloriseropositivity and age, sex, gastrointestinalcomplaints, medications, housing characteristics, and ABOor Lewis antigen status. CagA was positive in 84.5% ofinfected subjects. The average annual age-adjustedincidence of hospitalizations associated with diagnoses of peptic ulcer disease in Manitoba was higherfor treaty-status Indians (394.3/100,000) than fornon-Indians (203.8/100,000), but gastric cancer rateswere similar (11.2/100,000 vs 11.6/ 100,000). No H. pylori DNA was detected in the lake water. Inconclusion, the seroprevalence of CagA-positive H.pylori is high in this representative Manitoban Indiancommunity. This may be associated with an increased risk for peptic ulcer disease but is notassociated with an increased risk for gastriccancer.

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 Manitobas 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.

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 &ggr;, interleukin 2) and proliferation responses. Results:HIV controllers were characterized by elevated macrophage inflammatory protein 1&agr; and low levels of interferon &ggr;–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.

Epidemiological study of hepatitis B virus infection in Manitoba, Canada, 1992-2003.

In comparison with other Canadian provinces and most Western countries, the province of Manitoba maintains a different vaccination policy for hepatitis B. This policy provides selective antenatal screening for hepatitis B in women and an inoculation program for hepatitis B vaccination for fourth-grade pupils. There has been increasing concern for this policy with regard to its influence on secular trends of acute hepatitis B incidence in Manitoba. This created a need to summarise the epidemiological characteristics of hepatitis B virus (HBV) infection in Manitoba and to allocate finances and human resources for future prevention programs. The Cadham Provincial Laboratory in Winnipeg, a Canadian Public Health Laboratory, is responsible for testing all specimens for diagnosis of various common infectious diseases in Manitoba. During the period from 1 January 1992 to 31 December 2003, a total of 285,946 clinical specimens were submitted to this laboratory, which confirmed 310 cases of acute HBV and 7,556 cases of chronic HBV infection. A total of 18,168 individuals were identified as having vaccine-induced immune status. The incidence rate of acute HBV infection has significantly decreased from 6.52/100,000 person-years in 1996 to 0.86/100,000 person-years in 2003. Annual prevalence rates of chronic HBV infection in Manitoba increased slightly from 42.96 cases/100,000 population in 1992 to 71.47 cases/100,000 population in 2003. Incidence rates were generally higher in men than in women at all age groups, with values of 2.65 and 1.65 per 100,000 population, respectively (chi-square=15.768, p value <0.001). The highest incidence rate for both males and females was observed in the age group 30–34 years. The North Eastman and Winnipeg Regional Health Authorities showed significantly higher incidence rates of acute hepatitis B compared with the other nine Regional Health Authorities. Selective hepatitis B vaccination programs for children in Manitoba had achieved the greatest success in the prevention of vertical and horizontal transmission. There is an urgent need to develop cost-effective harm-reduction strategies for hepatitis B prevention among adults (aged 30–34) and groups at risk in Manitoba.

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 <

Serological studies of West Nile virus in a liver transplant population.

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 Winnipegs 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.