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Biomedical subjects

Cheryl A Jones

Publications and source records attributed to Cheryl A Jones.

13 recordsLinked to original sources
PubMed2006

Exposure to open tuberculosis on a neonatal unit.

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.

Adult↗
PubMed2005

Herpes simplex virus infection of human dendritic cells induces apoptosis and allows cross-presentation via uninfected dendritic cells.

HSV efficiently infects dendritic cells (DCs) in their immature state and induces down-regulation of costimulatory and adhesion molecules. As in mice, HSV infection of human DCs also leads to their rapid and progressive apoptosis, and we show that both early and late viral proteins contribute to its induction. Because topical HSV infection is confined to the epidermis, Langerhans cells are expected to be the major APCs in draining lymph nodes. However, recent observations in murine models show T cell activation to be mediated by nonepidermal DC subsets, suggesting cross-presentation of viral Ag. In this study we provide an explanation for this phenomenon, demonstrating that HSV-infected apoptotic DCs are readily phagocytosed by uninfected bystander DCs, which, in turn, stimulate virus-specific CD8+ T cell clones.

Antigen Presentation↗
PubMed2005

HSV induces an early primary Th1 CD4 T cell response in neonatal mice, but reduced CTL activity at the time of the peak adult response.

Neonates are highly susceptible to HSV. In this study, we analyzed the primary neonatal cell-mediated response to HSV at the site of T cell activation, the draining lymph nodes (LN), and examined the effects of dose and the ability of HSV to replicate on the strength and character of this response. Neonatal mice mounted a predominantly Th1 cytokine (IFN-gamma) response at all doses of a replication-competent thymidine kinase-negative HSV-2 strain (186DeltaKpn) and at high doses of a replication-defective HSV-2 virus (dl5-29, UL5(-)/UL29(-)). Both neonates and adults showed increased production of Th2 cytokines (IL-4 and/or IL-5) at high doses of the replication-defective or inactivated HSV strains. An age-dependent difference in the strength of the Th1 response was noted, with neonates mounting adult-like responses at low but not high doses of HSV. Neonatal mice also showed impaired CD8(+) T cell activation and reduced HSV-specific CTL effector function at the time of the peak adult response. These studies are the first to highlight the impaired primary neonatal T cell response to HSV in the LN.

Age Factors↗
PubMed2004

Vaccination strategies to prevent genital herpes and neonatal herpes simplex virus (HSV) disease.

Vaccination strategies to prevent genital and neonatal herpes simplex virus (HSV) disease have a history of apparent efficacy in animal studies followed by failure in clinical trials. Further study of the immune response induced by natural HSV infections in both adults and neonates will provide insight into the requirements for vaccination against acute disease and recurrences. Lessons can also be learnt from the recent partial success of a HSV-2 glycoprotein D vaccine coupled with monophosphoryl lipid A adjuvant, which induced protection from clinical disease in HSV-1 and HSV-2 seronegative women. Its efficacy has been attributed to enhancement of Th-1 immunity by the adjuvant. Newer vaccine vectors including DNA vaccines, recombinant viral vaccines and specific HSV mutants are being developed but better animal models are required for more rapid progress. This review examines the history of HSV vaccine development, describes recent progress towards an effective prophylactic vaccine against HSV and outlines further improvements required to make current vaccines immunogenic to a wide population.

Animals↗
PubMed2004

Epidemiological, clinical and laboratory aids for the diagnosis of neonatal herpes -- an Australian perspective.

Neonatal herpes is rare in Australia, possibly because of the older average age at pregnancy compared with other developed countries, low herpes simplex virus (HSV)-2 seroprevalence in the general community, low risk of HSV-2 acquisition during pregnancy and relatively high HSV-1 seroprevalence in adults. Guidelines on herpes management in pregnancy have been produced by the Australian Society for Infectious Diseases and endorsed by the Australian College of Obstetricians and Gynaecologists. However, diagnosing and managing neonatal infection remains difficult. Until an effective strategy to prevent neonatal herpes is developed, our efforts should focus on improving early diagnosis of HSV disease in the neonate and developing more effective strategies to reduce early reactivation and long-term morbidity.

Australia↗
PubMed2003

Development of prophylactic vaccines for genital and neonatal herpes.

Over five decades numerous conventional candidate live attenuated and killed vaccines have failed to prevent genital herpes in clinical trials. However, a vaccine consisting of recombinant glycoprotein D from herpes simplex virus (HSV)-2 and deacylated monophosphoryl lipid A adjuvant has recently shown partial efficacy against clinical disease transmitted from HSV-1 and -2 seronegative women (73-74%). Comparisons between the efficacy of this vaccine and previous failed candidates and their effects on the immune system should help guide development of better vaccines through selection of appropriate HSV proteins, adjuvants or cytokines and newer vaccine vectors, such as DNA vaccines, recombinant viral vaccines and specific HSV mutants.

Clinical Trials as Topic↗
PubMed2002

Maternal immunization with a herpes simplex virus type 2 replication-defective virus reduces visceral dissemination but not lethal encephalitis in newborn mice after oral challenge.

Herpes simplex virus (HSV) causes devastating infections in newborns. Maternal immunization is one potential strategy to reduce neonatal HSV disease. Female mice were immunized with an HSV type 2 (HSV-2) replication-defective mutant (HSV-2 dl5-29, which is defective for the genes UL5 and UL29) and then mated. Protection was evaluated in newborn mice after a virulent HSV-2 oral challenge. Heightened neonatal susceptibility was observed to a thymidine kinase-negative HSV-2 strain (HSV-2 186DeltaKpn) that is highly attenuated in adult mice. Maternal immunization with HSV-2 dl5-29 and HSV-2 186DeltaKpn reduced visceral spread of infectious challenge virus in pups after challenge at either 1 day or 1 week of age but did not prevent replication at the site of entry, spread to the central nervous system, or lethal encephalitis. No protection was seen in pups born to mock-immunized mothers or to mothers immunized with a UV-inactivated wild-type HSV-2 strain. Levels of protection correlated with levels of passively transferred maternal HSV-2-specific IgG antibody.

Animals↗
PubMed2002

Herpes simplex virus colitis in a neonate.

Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life.

Acyclovir↗
PubMedDate not supplied

Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials.

BACKGROUND: Antiviral prophylaxis is commonly used in recipients of solid-organ transplants with the aim of preventing the clinical syndrome associated with cytomegalovirus infection. We undertook a systematic review to investigate whether this approach affects risks of cytomegalovirus disease and death. METHODS: Randomised controlled trials of prophylaxis with antiviral medications for cytomegalovirus disease in solid-organ-transplant recipients were identified. Data were combined in meta-analyses by a random-effects model. FINDINGS: Compared with placebo or no treatment, prophylaxis with aciclovir, ganciclovir, or valaciclovir significantly reduced the risks of cytomegalovirus disease (19 trials, 1981 patients; relative risk 0.42 [95% CI 0.34-0.52]), cytomegalovirus infection (17 trials, 1786 patients; 0.61 [0.48-0.77]), and all-cause mortality (17 trials, 1838 patients; 0.63 [0.43-0.92]), mainly owing to lower mortality from cytomegalovirus disease (seven trials, 1300 patients; 0.26 [0.08-0.78]). Prophylaxis also lowered the risks of disease caused by herpes simplex or zoster virus, bacterial infections, and protozoal infections, but not fungal infection, acute rejection, or graft loss. Meta-regression showed no significant difference in the risk of cytomegalovirus disease or all-cause mortality by organ transplanted or cytomegalovirus serostatus; no conclusions were possible for cytomegalovirus-negative recipients of negative organs. In trials of direct comparisons, ganciclovir was more effective than aciclovir in preventing cytomegalovirus disease. Valganciclovir and intravenous ganciclovir were as effective as oral ganciclovir. INTERPRETATION: Prophylaxis with antiviral medications reduces the risk of cytomegalovirus disease and associated mortality in recipients of solid-organ transplants. This approach should be used routinely in cytomegalovirus-positive recipients and in cytomegalovirus-negative recipients of organs positive for the virus.

Acyclovir↗