%0 Journal Article
%~ PubMed
%A Scott, Gillian M
%A Chow, Sharon S W
%A Craig, Maria E
%A Pang, Chi N I
%A Hall, Beverley
%A Wilkins, Marc R
%A Jones, Cheryl A
%A Lloyd, Andrew R
%A Rawlinson, William D
%T Cytomegalovirus infection during pregnancy with maternofetal transmission induces a proinflammatory cytokine bias in placenta and amniotic fluid.
%B Journal of Infectious Diseases
%D 2012
%C United States
%I University of Chicago Press
%V 205
%N 8
%P 1305-1310
%@ 0022-1899
%X Congenital infection with cytomegalovirus (CMV) can induce immune responses and placental damage. By use of immunoassay panels, 27 cytokines were assessed in midtrimester amniotic fluid from 8 patients with congenital CMV, in midtrimester sera from 12 pregnant women with primary CMV infection, and in amniotic fluid and serum from uninfected maternal controls. Levels of the cytokines tumor necrosis factor ??, interleukin 1??, interleukin 12, and interleukin 17; the chemokines CCL2, CCL4, and CXCL10; and the growth factors granulocyte-macrophage colony-stimulating factor and platelet-derived growth factor bb were significantly elevated in amniotic fluid from congenital CMV patients (P < .01). Only CXCL10 was significantly higher in sera from CMV-infected pregnant women. CMV infection during pregnancy is associated with a shift in cytokine expression toward a proinflammatory state.
%Z FOR Codes: 111403 110804 111402


%0 Journal Article
%~ PubMed
%A Khandaker, Gulam
%A Zurynski, Yvonne
%A Buttery, Jim
%A Marshall, Helen
%A Richmond, Peter C
%A Dale, Russell C
%A Royle, Jenny
%A Gold, Michael
%A Snelling, Tom
%A Whitehead, Bruce
%A Jones, Cheryl
%A Heron, Leon
%A McCaskill, Mary
%A Macartney, Kristine
%A Elliott, Elizabeth J
%A Booy, Robert
%T Neurologic complications of influenza A(H1N1)pdm09: Surveillance in 6 pediatric hospitals.
%B Neurology
%D 2012
%C United States
%I Lippincott Williams & Wilkins
%V 79
%N 14
%P 1474-1481
%@ 1526-632X
%X 
%Z FOR Codes: 111403 60502 110902


%0 Journal Article
%~ PubMed
%A Marais, Ben
%A Crawford, John
%A Iredell, Jon
%A Ward, Michael
%A Simpson, Steve
%A Gilbert, Lyn
%A Griffiths, Paul
%A Kamradt-Scott, Adam
%A Colagiuri, Ruth
%A Jones, Cheryl
%A Sorrell, Tania
%T One world, one health: beyond the Millennium Development Goals.
%B Lancet
%D 2012
%C United Kingdom
%I The Lancet Publishing Group
%V 380
%N 9844
%P 805-806
%@ 0140-6736
%X 
%Z FOR Codes: 60502 60299 110899


%0 Journal Article
%~ PubMed
%A Caldwell, Patrina Hy
%A Oldmeadow, Wendy
%A Jones, Cheryl A
%T Supervisory needs of research doctoral students in a university teaching hospital setting.
%B Journal of Paediatrics and Child Health
%D 2012
%C United Kingdom
%I Wiley-Blackwell Publishing Ltd.
%V 48
%N 10
%P 907-912
%@ 1034-4810
%X Background/Hypothesis:??? Teaching hospitals affiliated with universities are now common sites for research higher degree supervision. We hypothesised that the hospital environment poses unique challenges to supervision compared with the traditional university research institute setting. Aims:??? This study aimed to identify and rank important supervision issues in a clinical setting from the students'' perspective. Methods:??? Using the Delphi method to explore issues and facilitate consensus, small group discussions were conducted with 10 research doctoral students from a tertiary teaching hospital. Results:??? We identified supervision issues that are unique to the hospital-based context. These include the demands placed on supervisors combining clinical and supervisory roles, the challenges of academic medical/scientific writing and career issues for students who are already established in their professions. Other issues identified, common to all doctoral students, include differing expectations between students and supervisors (with students wanting support for their career plans, training in research skills and increasing autonomy and responsibility), supervisor access, quality and frequency of meetings, lack of training in writing and dealing with conflicts. Conclusion:??? Our research identified that postgraduate students of supervisors who combine clinical and supervisory roles report significant issues with supervision, some of which are unique to the clinical setting. Clinician researchers who supervise postgraduate students need to balance clinical and supervisory responsibilities, identify and negotiate student expectations early in candidature and provide career counselling to students who are already highly experienced. Furthermore, clinician supervisors should undertake postgraduate supervisor training programme tailored to the hospital setting to better support their students.
%Z FOR Codes: 111403


%0 Journal Article
%~ PubMed
%A McCarthy, Fergus P
%A Giles, Michelle L
%A Rowlands, Shelley
%A Purcell, Kara J
%A Jones, Cheryl A
%T Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant.
%B Cochrane Database of Systematic Reviews
%D 2011
%C United Kingdom
%I John Wiley & Sons Ltd.
%V 2011
%N 3
%P CD008371
%@ 1469-493X
%X Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection.
%Z FOR Codes: 111704 110804 111403


%0 Journal Article
%~ PubMed
%A McMullan, Brendan J
%A Palasanthiran, Pamela
%A Jones, Cheryl A
%A Hall, Beverley M
%A Robertson, Peter W
%A Howard, Jonathan
%A Rawlinson, William D
%T Congenital cytomegalovirus - time to diagnosis, management and clinical sequelae in Australia: opportunities for earlier identification.
%B Medical Journal of Australia
%D 2011
%C Australia
%I Australasian Medical Publishing Company Pty. Ltd.
%V 194
%N 12
%P 625-629
%@ 1326-5377
%X To report on the burden of disease in Australian infants with congenital cytomegalovirus (cCMV) infection in the era of neonatal hearing screening and improved diagnostic techniques.
%Z FOR Codes: 111403 60506 111704


%0 Book Section
%A Jones, Cheryl
%T Congenital infection
%B Neonatalogy at a Glance 2nd edition
%D 2011
%C United States
%I Wiley-Blackwell Publishing Ltd.
%V 
%N 
%P 28-31
%@ 9781405199513
%E Lissauer, Tom
%E Fanaroff, Avroy A.
%X 
%Z FOR Codes: 111403 110703


%0 Book Section
%A Jones, Cheryl
%T Neonatal infection
%B Neonatalogy at a Glance 2nd edition
%D 2011
%C United States
%I Wiley-Blackwell Publishing Ltd.
%V 
%N 
%P 102-103
%@ 9781405199513
%E Lissauer, Tom
%E Fanaroff, Avroy A.
%X 
%Z FOR Codes: 111403 110309


%0 Book Section
%A Jones, Cheryl
%A Chivers, Jane
%T Promoting healthy sexual lives for young people with learning difficulties
%B Mental Health of Children and Adolescents with Intellectual and Developmental Disabilities: a Framework for Professional Practice
%D 2011
%C United States
%I IP Communications
%V 
%N 
%P 0
%@ 9780980864922
%E Dosseter, David
%E White, Donna
%E Whatson, Lesley
%X 
%Z FOR Codes: 111714 111704


%0 Book Section
%A Jones, Cheryl
%T Specific bacterial infections
%B Neonatalogy at a Glance 2nd edition
%D 2011
%C United States
%I Wiley-Blackwell Publishing Ltd.
%V 
%N 
%P 104-105
%@ 9781405199513
%E Lissauer, Tom
%E Fanaroff, Avroy A.
%X 
%Z FOR Codes: 111403 60501


%0 Book Section
%A Jones, Cheryl
%T Viral infections
%B Neonatalogy at a Glance 2nd edition
%D 2011
%C United States
%I Wiley-Blackwell Publishing Ltd.
%V 
%N 
%P 106-107
%@ 9781405199513
%E Lissauer, Tom
%E Fanaroff, Avroy A.
%X 
%Z FOR Codes: 60506 111403


%0 Journal Article
%~ PubMed
%A Ng, Lai Guan
%A Qin, Jim S
%A Roediger, Ben
%A Wang, Yilin
%A Jain, Rohit
%A Cavanagh, Lois L
%A Smith, Adrian L
%A Jones, Cheryl A
%A de Veer, Michael
%A Grimbaldeston, Michele A
%A Meeusen, Els N
%A Weninger, Wolfgang
%T Visualizing the Neutrophil Response to Sterile Tissue Injury in Mouse Dermis Reveals a Three-Phase Cascade of Events.
%B Journal of Investigative Dermatology
%D 2011
%C United Kingdom, United States
%I Nature Publishing Group
%V 131
%N 10
%P 2058-2068
%@ 1523-1747
%X Neutrophil granulocytes traffic into sites of organ injury in which they may not only participate in tissue repair and pathogen clearance but may also contribute to collateral cell damage through the release of noxious mediators. The dynamics and mechanisms of neutrophil migration in the extravascular space toward loci of tissue damage are not well understood. Here, we have used intravital multi-photon microscopy to dissect the behavior of neutrophils in response to tissue injury in the dermis of mice. We found that, following confined physical injury, initially rare scouting neutrophils migrated in a directional manner toward the damage focus. This was followed by the attraction of waves of additional neutrophils, and finally stabilization of the neutrophil cluster around the injury. Although neutrophil migration in the steady state and during the scouting phase depended on pertussis toxin-sensitive signals, the amplification phase was sensitive to interference with the cyclic adenosine diphosphate ribose pathway. We finally demonstrated that neutrophil scouts also transit through the non-inflamed dermis, suggesting immunosurveillance function by these cells. Together, our data unravel a three-step cascade of events that mediates the specific accumulation of neutrophils at sites of sterile tissue injury in the interstitial space.
%Z FOR Codes: 110707 110304


%0 Journal Article
%~ PubMed
%A Puttur, Franz K
%A Fernandez, Marian A
%A White, Rose
%A Roediger, Ben
%A Cunningham, Anthony L
%A Weninger, Wolfgang
%A Jones, Cheryl A
%T Herpes Simplex Virus Infects Skin {gamma}{delta} T Cells before Langerhans Cells and Impedes Migration of Infected Langerhans Cells by Inducing Apoptosis and Blocking E-Cadherin Downregulation.
%B Journal of immunology (Baltimore, Md. : 1950)
%D 2010
%C United States
%I American Association of Immunologists
%V 185
%N 1
%P 477-87
%@ 1550-6606
%X The role individual skin dendritic cell (DC) subsets play in the immune response to HSV remains unclear. We investigated the effect of HSV on DC virus uptake, viability, and migration after cutaneous infection in vitro and in vivo. HSV increased the emigration of skin DCs from whole skin explants over 3 d postinfection (p.i.) compared with mock controls, but the kinetics of emigration was influenced by the skin DC subset. Uninfected (bystander) Langerhans cells (LCs) were the major emigrant DC subset at 24 h p.i., but thereafter, large increases in infected CD103(+)langerin(+) dermal DC (dDC) and uninfected langerin(-) dDC emigration were also observed. LC infection was confirmed by the presence of HSV glycoprotein D (gD) and was associated with impaired migration from cultured skin. Langerin(+) dDC also expressed HSV gD, but infection did not impede migration. We then followed the virus in live MacGreen mice in which LCs express GFP using a fluorescent HSV-1 strain by time-lapse confocal microscopy. We observed a sequential infection of epidermal cells, first in keratinocytes and epidermal gammadelta T cells at 6 h p.i., followed by the occurrence of HSVgD(+) LCs at 24 h p.i. HSV induced CCR7 upregulation on all langerin(+) DC, including infected LCs, and increased production of skin TNF-alpha and IL-1beta. However, a large proportion of infected LCs that remained within the skin was apoptotic and failed to downregulate E-cadherin compared with bystander LCs or mock controls. Thus, HSV infection of LCs is preceded by infection of gammadelta T cells and delays migration.
%Z FOR Codes: 110804 110701 110304


%0 Journal Article
%~ PubMed
%A Muller, William J
%A Jones, Cheryl A
%A Koelle, David M
%T Immunobiology of herpes simplex virus and cytomegalovirus infections of the fetus and newborn.
%B Current Immunology Reviews
%D 2010
%C Netherlands
%I Bentham Science Publishers Ltd.
%V 6
%N 1
%P 38-55
%@ 1573-3955
%X Immunologic "immaturity" is often blamed for the increased susceptibility of newborn humans to infection, but the precise mechanisms and details of immunologic development remain somewhat obscure. Herpes simplex virus (HSV) and cytomegalovirus (CMV) are two of the more common severe infectious agents of the fetal and newborn periods. HSV infection in the newborn most commonly occurs after exposure to the virus during delivery, and can lead to a spectrum of clinical disease ranging from isolated skin-eye-mucous membrane infection to severe disseminated multiorgan disease, often including encephalitis. In contrast to HSV, clinically severe CMV infections early in life are usually acquired during the intrauterine period. These infections can result in a range of clinical disease, including hearing loss and neurodevelopmental delay. However, term newborns infected with CMV after delivery are generally asymptomatic, and older children and adults often acquire infection with HSV or CMV with either no or mild clinical symptoms. The reasons for these widely variable clinical presentations are not completely understood, but likely relate to developmental differences in immune responses.This review summarizes recent human and animal studies of the immunologic response of the fetus and newborn to these two infections, in comparison to the responses of older children and adults. The immunologic defense of the newborn against each virus is considered under the broader categories of (i) the placental barrier to infection, (ii) skin and mucosal barriers (including antimicrobial peptides), (iii) innate responses, (iv) humoral responses, and (v) cellular responses. A specific focus is made on recent studies of innate and cellular immunity to HSV and CMV.
%Z FOR Codes: 110701 110804 111401


%0 Journal Article
%A Jones, Cheryl
%T Systemic herpes infections
%B Paediatrics and Child Health
%D 2010
%C United Kingdom
%I The Medicine Publishing Company
%V 20
%N 11
%P 521-525
%@ 1751-7222
%X 
%Z FOR Codes: 111403 60506


%0 Journal Article
%~ PubMed
%A Cunningham, Anthony L
%A Abendroth, Allison
%A Jones, Cheryl
%A Nasr, Najla
%A Turville, Stuart
%T Viruses and Langerhans cells.
%B Immunology and cell biology
%D 2010
%C United Kingdom, Australia
%I Nature Publishing Group
%V 88
%N 4
%P 416-23
%@ 0818-9641
%X Langerhans cells (LCs) are the resident dendritic cells (DCs) of epidermis in human mucosal stratified squamous epithelium and the skin. A phenotypically similar DC has recently been discovered as a minor population in the murine dermis. In epidermis, LCs function as sentinel antigen-presenting cells that can capture invading viruses such as herpes simplex virus (HSV), varicella-zoster virus (VZV) and human immunodeficiency virus (HIV). This interaction between LCs and viruses results in highly variable responses, depending on the virus as discussed in this review. For example, HSV induces apoptosis in LCs but HIV does not. LCs seem to be the first in a complex chain of antigen presentation to T cells in lymph nodes for HSV and possibly VZV, or they transport virus to T cells, as described for HIV and maybe VZV. Together with epidermal keratinocytes they may also have a role in the initial innate immune response at the site of infection in the epidermis, although this is not fully known. The full spectrum of biological responses of LCs even to these viruses has yet to be understood and will require complementary studies in human LCs in vitro and in murine models in vivo.
%Z FOR Codes: 110804 110707


%0 Journal Article
%~ Isi
%A Giles, M. L.
%A Pedrana, A.
%A Jones, C.
%A Garland, S.
%A Hellard, M.
%A Lewin, S. R.
%T Antenatal screening practice for infectious diseases by general practitioners in Australia
%B Australian & New Zealand Journal of Obstetrics & Gynaecology
%D 2009
%C Australia
%I Wiley-Blackwell Publishing Asia
%V 49
%N 1
%P 39-44
%@ 0004-8666
%X 
%Z FOR Codes: 60502 111401 111708


%0 Journal Article
%~ PubMed
%A Jones, Cheryl A
%A Walker, Karen S
%A Badawi, Nadia
%T Antiviral agents for treatment of herpes simplex virus infection in neonates.
%B Cochrane Database of Systematic Reviews
%D 2009
%C United Kingdom
%I Update Software Ltd.
%V 0
%N 3
%P CD004206
%@ 1469-493X
%X BACKGROUND: Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae. OBJECTIVES: To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression. SEARCH STRATEGY: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI). MAIN RESULTS: Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period. AUTHORS'' CONCLUSIONS: There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.
%Z FOR Codes: 111403 60599


%0 Journal Article
%~ PubMed
%A Blyth, Christopher
%A Best, Emma
%A Jones, Cheryl
%A Nourse, Clare
%A Goldwater, Paul
%A Daley, Andrew
%A Burgner, David
%A Henry, Guy
%A Palasanthiran, Pamela
%T Nontuberculous Mycobacterial Infection in Children: A Prospective National Study.
%B The Pediatric infectious disease journal
%D 2009
%C United States, Netherlands
%I Lippincott Williams & Wilkins
%V 28
%N 9
%P 801-5
%@ 0891-3668
%X The epidemiology and management of nontuberculous mycobacterial (NTM) infection in Australian children is unknown.
%Z FOR Codes: 60501 111403


%0 Journal Article
%~ PubMed
%A Jones, Cheryl A
%T Vertical transmission of genital herpes: prevention and treatment options.
%B Drugs
%D 2009
%C New Zealand
%I Adis International Ltd.
%V 69
%N 4
%P 421-434
%@ 0012-6667
%X Herpes simplex virus (HSV) transmitted from mother to child around the time of delivery can cause potentially fatal disease in the newborn. Women who experience their first genital HSV infection in pregnancy are at the highest risk of transmitting the virus to their newborn. Efforts to prevent vertically transmitted HSV disease can be directed in the following three ways: (i) prevent maternal genital HSV infection; (ii) prevent transmission during pregnancy and delivery; or (iii) postnatally prevent disease in an exposed newborn. Oral aciclovir and valaciclovir given prophylactically in late pregnancy have been shown to limit clinical recurrence of genital herpes, shedding of HSV at delivery and the rate of caesarean delivery for past HSV disease. However, there are insufficient data to determine the effect of oral antiviral prophylaxis in pregnancy on neonatal HSV disease. Neonatal HSV disease should always be treated with systemic antiviral therapy. There is currently no vaccine licensed to prevent genital herpes, although a number show promise in clinical trials. The role of intrapartum antiviral therapy and postnatal strategies to prevent neonatal HSV disease require further evaluation.
%Z FOR Codes: 60599


%0 Journal Article
%~ PubMed
%A Chow, Sharon S W
%A Craig, Maria E
%A Jones, Cheryl A
%A Hall, Beverley
%A Catteau, Jacki
%A Lloyd, Andrew R
%A Rawlinson, William D
%T Differences in amniotic fluid and maternal serum cytokine levels in early midtrimester women without evidence of infection.
%B Cytokine
%D 2008
%C United Kingdom
%I Academic Press
%V 44
%N 1
%P 78-84
%@ 1096-0023
%X The amniotic fluid cytokine profile has been shown to be indicative of various disease states, and changes may be associated with preterm labor or infection. Anti-inflammatory cytokine profiles may be essential for successful normal pregnancy. However, there are currently few normative data on the concentration of cytokines in amniotic fluids during pregnancy. The aim of this study was to provide new amniotic fluid cytokine data for future comparative studies in disease states, notably in utero viral infections, and to compare these with maternal serum levels. Amniotic fluid was obtained from 100 pregnant women undergoing elective amniocentesis at the Royal Hospital for Women, Randwick. Concentrations of 27 cytokines were simultaneously measured in amniotic fluid and a subset of matching maternal sera (n=33) using a multiplex bead-based immunoassay system (Bio-Plex, Bio-Rad). To exclude infection, nested multiplex PCR targeting 17 known congenital infectious agents were performed on all amniotic fluid and maternal serum samples, and serological testing was also performed against some of these agents. Maternal serum concentration was positively correlated with amniotic fluid levels for MIP-1beta (r=0.39, P=0.027). IL-1ra was positively correlated to maternal age (r=0.210, P=0.036), and mean IL-5 levels were significantly higher in amniotic fluids from pregnancies with male fetuses than those with female fetuses (P=0.036). Normal amniotic fluid concentrations for five cytokines (IL-6, IL-8, IP-10, MCP-1, IL-1ra) were found to be significantly elevated over maternal serum concentrations in matched pairs (P<0.05). Concentrations of 12 cytokines (eotaxin, IFN-gamma, IL-9, IL-12, IL-15, IL-17, MIP-1alpha, MIP-1beta, RANTES, TNF-alpha, VEGF, PDGF bb) were significantly elevated in maternal serum compared to paired amniotic fluid at midtrimester (P<0.05). Amniotic fluid may be more representative of the fetal cytokine profile than cytokine analysis on antenatal sera as it represents predominantly fetal urinary and respiratory secretions. This study provides new normative data for multiple cytokine levels in amniotic fluid and maternal sera at 14-16 weeks gestation, and is a valuable tool for future diagnostic and comparative studies.
%Z FOR Codes: 110804 111401 110701


%0 Book Section
%A Jones, Cheryl
%T Infections in the critically ill Neonate
%B Infectious Diseases in the Pediatric Intensive Care Unit
%D 2008
%C United Kingdom
%I Springer
%V 
%N 
%P 59-96
%@ 978-1-8462-8916-3
%E Nadel, Simon
%X 
%Z FOR Codes: 1114


%0 Journal Article
%~ PubMed
%A Fernandez, Marian A
%A Evans, Ingrid A C
%A Hassan, Eddy H
%A Carbone, Francis R
%A Jones, Cheryl A
%T Neonatal CD8+ T cells are slow to develop into lytic effectors after HSV infection in vivo.
%B European journal of immunology
%D 2008
%C Germany
%I Wiley - VCH Verlag GmbH & Co. KGaA
%V 38
%N 1
%P 102-113
%@ 0014-2980
%X HSV is an important neonatal pathogen. We defined the kinetics of the primary CTL response to HSV-2 in vivo in neonatal mice. Using a replication-defective HSV-2 virus, we demonstrate that neonates mount a primary HSV-specific CTL effector response in the draining LN, with delayed onset and shortened peak activity, in contrast to the rapid, strong response observed in adult mice. The shortened peak neonatal CTL response is independent of HSV dose and is associated with retarded CD8(+) T cell expansion, reduced expansion of HSV-specific tetramer-positive CD8(+) T cells and a reduced CD8(+) T cell IFN-gamma response. Paradoxically, neonatal CD8(+) T cells display enhanced non-specific early activation that is not sustained. Neonatal HSV-specific TCR-transgenic CD8(+) T cells showed reduced proliferation in vivo when transferred into HSV-infected neonatal mice compared to adult T cell controls. Our data suggest that early events in CD8(+) T cell priming underlie the attenuated newborn CTL response to HSV.
%Z FOR Codes: 110704 111403 110804


%0 Journal Article
%~ PubMed
%A Fernandez, Marian A
%A Puttur, Franz K
%A Wang, Yuan M
%A Howden, Wade
%A Alexander, Stephen I
%A Jones, Cheryl A
%T T regulatory cells contribute to the attenuated primary CD8+ and CD4+ T cell responses to herpes simplex virus type 2 in neonatal mice.
%B Journal of Immunology
%D 2008
%C United States
%I American Association of Immunologists
%V 180
%N 3
%P 1556-1564
%@ 0022-1767
%X The first weeks of life are characterized by immune tolerance and increased susceptibility to intracellular pathogens. The neonatal adaptive response to HSV is attenuated compared with adult control models in humans and mice. T Regulatory cells (Tregs) control autoimmunity and excessive immune responses to infection. We therefore compared Treg responses in the draining lymph nodes (LN) of HSV-infected neonatal and adult C57BL/6 mice with the effect of Treg depletion/inactivation by anti-CD25 (PC61) treatment before infection on Ag-specific T cell effector responses at this site. There was a small, but significant increase in the frequency of CD4(+)Foxp3(+) Tregs at day 3 postinfection (p.i.) in the LN of neonatal and adult mice, compared with age-matched mock-infected controls. Depletion of Tregs before HSV infection significantly enhanced HSV-specific CD8(+) T cell cytotoxicity in vivo, cell number, activation, and granzyme B expression 4 days p.i. only in neonatal mice, and significantly enhanced CD8(+) and CD4(+) T cell IFN-gamma responses in both infected adults and neonates. Treg depletion also reduced the titer of infectious virus in the draining LN and nervous system of infected neonates on days 2 and 3 p.i. Treg suppression of the neonatal CTL response p.i. with HSV was associated with increased expression of TGF-beta in the draining LN at day 4 p.i. compared with uninfected neonates, but IL-10 was increased in infected adults alone. These experiments support the notion that the newborn primary T cell effector responses to HSV are suppressed by Tregs.
%Z FOR Codes: 110701


%0 Journal Article
%~ PubMed
%A Rawlinson, W D
%A Hall, B
%A Jones, C A
%A Jeffery, H E
%A Arbuckle, S M
%A Graf, N
%A Howard, J
%A Morris, J M
%T Viruses and other infections in stillbirth: what is the evidence and what should we be doing?
%B Pathology
%D 2008
%C 655 Avenue Of The Americas, New York, Ny, 10010
%I Elsevier Science Inc
%V 40
%N 2
%P 149-160
%@ 0031-3025
%X In Australia, as in other developed countries, approximately 40-50% of stillbirths are of unknown aetiology. Emerging evidence suggests stillbirths are often multifactorial. The absence of a known cause leads to uncertainty regarding the risk of recurrence, which can cause extreme anguish for parents that may manifest as guilt, anger or bewilderment. Further, clinical endeavours to prevent recurrences in future pregnancies are impaired by lack of a defined aetiology. Therefore, efforts to provide an aetiological diagnosis of stillbirth impact upon all aspects of care of the mother, and inform many parts of clinical decision making. Despite the magnitude of the problem, that is 7 stillbirths per 1000 births in Australia, diagnostic efforts to discover viral aetiologies are often minimal. Viruses and other difficult to culture organisms have been postulated as the aetiology of a number of obstetric and paediatric conditions of unknown cause, including stillbirth. Reasons forwarded for testing stillbirth cases for infectious agents are non-medical factors, including addressing all parents'' need for diagnostic closure, identifying infectious agents as a sporadic cause of stillbirth to reassure parents and clinicians regarding risk for future pregnancies, and to reduce unnecessary testing. It is clear that viral agents including rubella, human cytomegalovirus (CMV), parvovirus B19, herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV), and varicella zoster virus (VZV) may cause intrauterine deaths. Evidence for many other agents is that minimal or asymptomatic infections also occur, so improved markers of adverse outcomes are needed. The role of other viruses and difficult-to-culture organisms in stillbirth is uncertain, and needs more research. However, testing stillborn babies for some viral agents remains a useful adjunct to histopathological and other examinations at autopsy. Modern molecular techniques such as multiplex PCR, allow searches for multiple agents. Now that such testing is available, it is important to assess the clinical usefulness of such testing.
%Z FOR Codes: 111402 111404 111401


%0 Journal Article
%~ PubMed
%A Hodson, E M
%A Jones, C A
%A Strippoli, G F M
%A Webster, A C
%A Craig, J C
%T Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients.
%B Cochrane database of systematic reviews (Online)
%D 2007
%C United Kingdom.
%I Update Software Ltd.
%V 0
%N 2
%P CD005129
%@ 1469-493X
%X BACKGROUND: Cytomegalovirus (CMV) is the most common virus causing disease and death in solid organ transplant recipients during the first six months post-transplant. Previous systematic reviews have demonstrated the efficacy of antiviral medications used prophylactically or pre-emptively in preventing CMV disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti CMV vaccines and interferon) are examined. OBJECTIVES: To assess the benefits and harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV disease in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Renal Group''s Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction.Date of last search: December 2005 SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing IgG, anti CMV vaccine or interferon with placebo or no treatment, IgG alone or combined with antiviral medications with antiviral medications or IgG alone in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Two of four authors independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Thirty seven trials (2185 participants) were included in this review. There was no significant difference in the risk for CMV disease (16 trials, 770 patients: RR 0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95% CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI 0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG significantly reduced the risk of death from CMV disease (6 trials, 346 patients: RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4 trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2 trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication combined with IgG and antiviral medication alone. There was no significant difference in the risk of CMV disease with anti CMV vaccine or interferon compared with placebo or no treatment. AUTHORS'' CONCLUSIONS: Currently there are no indications for IgG in the prophylaxis of CMV disease in recipients of solid organ transplants.
%Z FOR Codes: 110804 111716


%0 Journal Article
%~ PubMed
%A Isaacs, David
%A Jones, Cheryl A
%A Dalton, Dianne
%A Cripps, Terri
%A Vidler, Leanne
%A Rochefort, Marilyn
%A Bide, Elizabeth
%A Banner, Pam
%A Crawford, Hamish
%T Exposure to open tuberculosis on a neonatal unit.
%B Journal of paediatrics and child health
%D 2006
%C Australia
%I Blackwell Publishing Asia
%V 42
%N 9
%P 557-9
%@ 1034-4810
%X The mother of a baby on the neonatal intensive care unit was found to have untreated open pulmonary tuberculosis. Tuberculin skin testing and chemoprophylaxis was offered to selected mothers and babies, depending on level of exposure. One of 3 mothers sharing a room with the index mother and 2 of 20 mothers whose babies were on the neonatal unit subsequently converted to tuberculin and were given isoniazid chemoprophylaxis. Isoniazid chemoprophylaxis was given to 13 exposed babies, none of whom tuberculin converted. Two babies were treated empirically for tuberculosis.
%Z FOR Codes: 111716 110802


%0 Journal Article
%~ PubMed
%A Strippoli, G F
%A Hodson, E M
%A Jones, C J
%A Craig, J C
%T Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients.
%B Cochrane database of systematic reviews (Online : Update Software)
%D 2006
%C UK
%I Update Software Ltd
%V 25
%N 1
%P CD005133
%@ 1469-493X
%X BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment with antiviral agents of patients with CMV viraemia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease. OBJECTIVES: This review was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference lists and conference proceedings were searched. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no treatment or antiviral prophylaxis in solid organ transplant recipients. DATA COLLECTION AND ANALYSIS: Two authors assessed the quality and extracted all data. Analysis was with a random-effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Ten eligible trials (476 patients) were identified, six of pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), three of pre-emptive treatment versus antiviral prophylaxis and one of oral versus intravenous pre-emptive treatment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease, acute rejection or all-cause mortality. AUTHORS'' CONCLUSIONS: Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.
%Z FOR Codes: 110804 110309 111716


%0 Journal Article
%~ PubMed
%A Strippoli, Giovanni F M
%A Hodson, Elisabeth M
%A Jones, Cheryl
%A Craig, Jonathan C
%T Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients.
%B Transplantation
%D 2006
%C United States
%I Lippincott Williams & Wilkins
%V 81
%N 2
%P 139-145
%@ 0041-1337
%X BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Preemptive treatment with antiviral agents of patients with CMV viremia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease. This study was conducted to evaluate the efficacy of preemptive treatment in preventing symptomatic CMV disease. METHODS: The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of preemptive treatment in solid organ transplant recipients. Two authors extracted all data; analysis was with a random effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Ten eligible trials (476 patients) were identified, six of preemptive treatment versus placebo or standard care (treatment of CMV when disease occurred), three of preemptive treatment versus antiviral prophylaxis and one of oral versus intravenous preemptive treatment. Compared with placebo or standard care, preemptive treatment significantly reduced the risk of CMV disease (6 trials, 288 patients, RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 trials, 185 patients, RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (2 trials, 176 patients, RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of preemptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease (2 trials, 151 patients, RR 0.42, 95% CI 0.07 to 2.65), acute rejection (1 trial, 70 patients, RR 0.94, 95% CI 0.42 to 2.09) or all-cause mortality (3 trials, 151 patients, RR 1.86, 95% CI 0.61 to 5.72). CONCLUSIONS: Few randomized trials have evaluated the effects of preemptive therapy to prevent CMV disease. Preemptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of preemptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.
%Z FOR Codes: 110708


%0 Journal Article
%~ PubMed
%A Cunningham, Anthony L
%A Diefenbach, Russell J
%A Miranda-Saksena, Monica
%A Bosnjak, Lidija
%A Kim, Min
%A Jones, Cheryl
%A Douglas, Mark W
%T The cycle of human herpes simplex virus infection: virus transport and immune control.
%B The Journal of infectious diseases
%D 2006
%C United States
%I University of Chicago Press
%V 194 Suppl 1
%N 
%P S11-8
%@ 0022-1899
%X After infection of skin or mucosa, herpes simplex virus enters the sensory nerve endings and is conveyed by retrograde axonal transport to the dorsal root ganglion, where the virus develops lifelong latency. Intermittent reactivation, which is spontaneous in humans, leads to anterograde transport of virus particles and proteins to the skin or mucosa, where the virus is shed and/or causes disease. Immune control of viral infection and replication occurs at the level of skin or mucosa during initial or recurrent infection and also within the dorsal root ganglion, where immune mechanisms control latency and reactivation. This article examines current views on the mechanisms of retrograde and anterograde transport of the virus in axons and the mechanisms of innate and adaptive immunity that control infection in the skin or mucosa and in the dorsal root ganglion--in particular, the role of interferons, myeloid and plasmacytoid dendritic cells, CD4(+) and CD8(+) T cells, and interferon- gamma and other cytokines, including their significance in the development of vaccines for genital herpes.
%Z FOR Codes: 110804


%0 Journal Article
%~ PubMed
%A Hardikar, Winita
%A Elliott, Elizabeth J
%A Jones, Cheryl A
%T The silent infection: should we be testing for perinatal hepatitis C and, if so, how?
%B The Medical journal of Australia
%D 2006
%C Australia
%I Australasian Medical Publishing Company Pty. Ltd.
%V 184
%N 2
%P 54-5
%@ 0025-729X
%X We recommend screening all infants whose mothers are HCV antibody-positive.
%Z FOR Codes: 110804 110307 110309