Infectious Diseases - Research Publications

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    Working with West African migrant communities on HIV prevention in Australia
    Lemoh, C ; Biggs, B-A ; Hellard, M (CSIRO Publishing, 2008-11-18)
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    Delayed diagnosis of HIV infection in Victoria 1994 to 2006
    Lemoh, C ; Guy, R ; Yohannes, K ; Lewis, J ; Street, A ; Biggs, B ; Hellard, M (CSIRO PUBLISHING, 2009)
    BACKGROUND: The identification of factors associated with delayed diagnosis of HIV infection in Victoria, Australia was the aim of the present study. METHODS: Demographic and epidemiological characteristics of cases notified to the Victorian HIV surveillance database between 1 January 1994 and 31 December 2006 were analysed. Delayed diagnosis was defined as: CD4 count below 200 cells mm(-3) at HIV diagnosis or diagnosis of AIDS earlier than 3 months after HIV diagnosis. RESULTS: Diagnosis of HIV was delayed in 627 (22.6%) of 2779 cases. Of these, 528 (84.2%) had either a high-risk exposure or were born in a high-prevalence country. The most common exposure was male homosexual contact in 64.3% of cases. Independent risk factors for delayed diagnosis were: older age at diagnosis (30-39 years odds ratio [OR] 2.15, > or = 50 years OR 7.50, P < 0.001), exposure via routes other than male homosexual sex or injecting drug use (heterosexual sex OR 2.51, P < 0.001, unknown/other route OR 4.24, P < 0.001); birth in Southern/Eastern Europe (OR 2.54), South-east Asia (OR 2.70) or the Horn of Africa/North Africa (OR 3.71, P < 0.001), and male gender (OR 0.47 for females, P < 0.001). CONCLUSION: Delay in the diagnosis of HIV infection is common in Victoria, but potentially avoidable in the majority of cases. Most people with delayed diagnosis had a history of male homosexual contact, injecting drug use, birth in a high-prevalence country or sexual contact with such individuals. An accurate sexual history, together with knowledge of their country of birth, should identify most individuals who should be offered an HIV test.
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    Heterosubtypic T-cell responses against avian influenza H5 haemagglutinin are frequently detected in individuals vaccinated against or previously infected with human subtypes of influenza
    Goy, K ; Von Bibra, S ; Lewis, J ; Laurie, K ; Barr, I ; Anderson, D ; Hellard, M ; Ffrench, R (WILEY, 2008-07)
    BACKGROUND: Cellula r immune responses play a critical role in providing help for the production of neutralizing antibodies to influenza virus, as well as producing anti-viral cytokines and killing infected cells in the lung. Heterosubtypic T-cell responses between different subtypes of influenza have been shown to exist in humans and to provide protection against morbidity and mortality associated with H5N1 infection in animal challenge models. Therefore, existing T-cell responses induced by natural infection or vaccination in humans may provide some degree of protection from infection with H5N1 strains, or may attenuate the severity of disease. OBJECTIVES: To investigate heterosubtypic T-cell responses to avian influenza in humans. METHODS: T-cell responses to an overlapping set of H5 HA peptides and inactivated viruses (H1N1, H3N2 and H5N1) were assessed using IFN-gamma and IL-2 enzyme-linked immunospot (ELISpot) assays in a cohort of adults either vaccinated against seasonal influenza in the last 3 years (n = 20) or previously infected (n = 40). RESULTS: T-cell responses to all three subtypes of virus were found in both infected and vaccinated individuals by IFN-gamma and IL-2 ELISpot assays. Approximately half of the participants from each group had a positive T-cell response to the H5 HA peptides in the IFN-gamma or IL-2 ELISpot assay. CONCLUSIONS: Heterosubtypic T-cell responses to H5 HA occur quite frequently in vaccinated and infected individuals. Further investigation of these responses and what role they may play upon challenge or vaccination against H5N1 may assist in vaccine design for avian influenza.
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    Fecal colonization with vancomycin-resistant enterococci in Australia
    Padiglione, AA ; Grabsch, EA ; Olden, D ; Hellard, M ; Sinclair, MI ; Fairley, CK ; Grayson, ML (CENTER DISEASE CONTROL, 2000)
    To assess the rate of fecal vancomycin-resistant enterococci (VRE) colon ization in Austalia, we examined specimens from 1,085 healthy volunteers. VRE was cultured from 2(0.2%) of 1,085 specimens; both were vanB Enter ococcus faecium, identical by pulsed-field gel electrophoresis, but with a pattern rare in Melbourne hospitals.
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    A randomized, blinded, controlled trial investigating the gastrointestinal health effects of drinking water quality
    Hellard, ME ; Sinclair, MI ; Forbes, AB ; Fairley, CK (US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE, 2001-08)
    A double-blinded, randomized, controlled trial was carried out in in Melbourne, Australia, to determine the contribution of drinking water to gastroenteritis. Melbourne is one of the few major cities in the world that draws drinking water from a protected forest catchment with minimal water treatment (chlorination only). Six hundred families were randomly allocated to receive either real or sham water treatment units (WTUs) installed in their kitchen. Real units were designed to remove viruses, bacteria, and protozoa. Study participants completed a weekly health diary reporting gastrointestinal symptoms during the 68-week observation period. There were 2,669 cases of highly credible gastroenteritis (HCG) during the study (0.80 cases/person/year). The ratio of HCG episode rates for the real WTU group compared to the sham WTU group was 0.99 (95% confidence interval, 0.85-1.15, p = 0.85). We collected 795 fecal specimens from participants with gastroenteritis, and pathogens were not more significantly common in the sham WTU group. We found no evidence of waterborne disease in Melbourne. The application of this methodology to other water supplies will provide a better understanding of the relationship between human health and water quality.
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    Analysis of FOXP3+ Regulatory T Cells That Display Apparent Viral Antigen Specificity during Chronic Hepatitis C Virus Infection
    Li, S ; Floess, S ; Hamann, A ; Gaudieri, S ; Lucas, A ; Hellard, M ; Roberts, S ; Paukovic, G ; Plebanski, M ; Loveland, BE ; Aitken, C ; Barry, S ; Schofield, L ; Gowans, EJ ; John, WE (PUBLIC LIBRARY SCIENCE, 2009-12)
    We reported previously that a proportion of natural CD25(+) cells isolated from the PBMC of HCV patients can further upregulate CD25 expression in response to HCV peptide stimulation in vitro, and proposed that virus-specific regulatory T cells (Treg) were primed and expanded during the disease. Here we describe epigenetic analysis of the FOXP3 locus in HCV-responsive natural CD25(+) cells and show that these cells are not activated conventional T cells expressing FOXP3, but hard-wired Treg with a stable FOXP3 phenotype and function. Of approximately 46,000 genes analyzed in genome wide transcription profiling, about 1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive natural CD25(+) cells and conventional T cells. Expression profiles, including cell death, activation, proliferation and transcriptional regulation, suggest a survival advantage of HCV-responsive Treg over the other cell populations. Since no Treg-specific activation marker is known, we tested 97 NS3-derived peptides for their ability to elicit CD25 response (assuming it is a surrogate marker), accompanied by high resolution HLA typing of the patients. Some reactive peptides overlapped with previously described effector T cell epitopes. Our data offers new insights into HCV immune evasion and tolerance, and highlights the non-self specific nature of Treg during infection.