Infectious Diseases - Research Publications
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ItemPI3K Activation in Neural Stem Cells Drives Tumorigenesis which can be Ameliorated by Targeting the cAMP Response Element Binding (CREB) Protein(Oxford University Press, 2018-10)BACKGROUND: Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling is common in cancers, but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells (NSPCs), where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. METHODS: To investigate the role of the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, phosphatase and tensin homolog (PTEN), to NSPCs. RESULTS: Expression of a Pik3caH1047A was sufficient to generate tumors with oligodendroglial features, but simultaneous loss of PTEN was required for the development of invasive, high-grade glioma. Pik3caH1047A-PTEN mutant NSPCs exhibited enhanced neurosphere formation which correlated with increased Wnt signaling, while loss of cAMP response element binding protein (CREB) in Pik3caH1047A-Pten mutant tumors led to longer symptom-free survival in mice. CONCLUSION: Taken together, our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis and that disruption of downstream CREB signaling attenuates tumor expansion.
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ItemNo Preview AvailableCorrection: Does Malaria Affect Placental Development? Evidence from In Vitro Models(Public Library of Science (PLoS), 2013)
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ItemNo Preview AvailableEvaluation of Haemophilus influenzae Type b Vaccine for Routine Immunization in Nepali Infants(Wolters Kluwer Health, 2012-04)BACKGROUND: Haemophilus influenzae type b (Hib) carriage and disease studies in Nepali children suggest a significant burden of infection. Hib conjugate vaccines (HibCV) do not have uniform immunogenicity between populations. We determined the immunogenicity of HibCV in Nepali infants, before its introduction into the routine immunization schedule. METHODS: Ninety infants recruited at Patan Hospital, Kathmandu, received 3 doses of the HibCV with routine immunizations (diphtheria, tetanus, whole cell pertussis-hepatitis B vaccine + oral polio vaccine) at 6, 10 and 14 weeks of age, and a HibCV booster at 52 weeks. Anti-polyribosylribitol phosphate (PRP) concentrations were measured at 18, 52 and 56 weeks, and the antibody persistence at 52 weeks was compared with antibody values in unimmunized controls (n = 30). RESULTS: After 3 doses of primary immunizations, at 18 weeks of age (n = 74), all infants had anti-PRP concentrations above the accepted thresholds for short- and long-term protection (0.15 and 1.0 µg/mL, respectively). At 1 year of age, before administration of the booster of HibCV, the anti-PRP geometric mean antibody concentration was 2.76 µg/mL (confidence interval: 1.88-4.07) in sera from the immunized children compared with 0.11 µg/mL (95% confidence interval: 0.08-0.17) in the nonimmunized control group (n = 30). Twenty-seven percent (20/74) of participants, however, had anti-PRP concentrations <1.0 µg/mL. Four weeks after the booster dose of HibCV, 98.5% of infants had anti-PRP concentrations above 1.0 µg/mL. CONCLUSION: Immunization with HibCV given as part of the Expanded Program on Immunization schedule in Nepal elicits robust antibody responses. Though the antibody wanes during the first year of life, most 1-year-old infants remain protected and respond robustly to a booster dose of the vaccine.
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ItemNo Preview AvailableCerebral phaeohyphomycosis caused by Cladophialophora bantiana in a patient with chronic lymphocytic leukemia(Elsevier, 2006-07-15)The phaeohyphomycoses are infections caused by dematiaceous fungi. The dark pigmentation results from the melanin in their cell walls, which may be one of the factors responsible for the virulence and pathogenic potential of these fungi (1). Cladophialophora bantiana is highly neurotropic and accounts for the majority of cases of cerebral phaeohyphomycosis. Unlike many of the opportunistic fungi, most reported cases of cerebral phaeohyphomycosis caused by C. bantiana have occurred in immunocompetent patients. C. bantiana infection is often reported as being resistant to conventional medical therapy and as having an overall poor prognosis, regardless of immune status. Medical therapy is not standardized, and clinical experience with the newer azoles, such as voriconazole, has been limited.
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ItemNo Preview AvailableBrain tumours in infancy: a clinicopathological study(Elsevier, 1997-04)To investigate the clinicopathological features of brain tumours occurring in the first year of life, the records of the Department of Histopathology at the Adelaide Children's Hospital were examined for cases where the initial diagnosis of intracranial neoplasm had been made in infancy. Surgical material was available for review from 1972 to 1993 and autopsy cases were reviewed for an additional 12 years from 1962 to 1993. Twenty-four infants with intracranial neoplasms were diagnosed ranging in age from 5 days to 1 year (average = 7 months). There were 23 surgical cases and 1 autopsy case. The male to female ratio was 17:7. Fifty-eight percent of the tumours were located in the supratentorial region. Although the incidence is relatively low, this study demonstrates that a wide range of brain tumours, which differ significantly in both clinical presentation and location from those found in the older child, do occur during the first year of life. The location of the primary tumour may be affected by associated congenital malformations, and metastatic malignancy, although rare, may occur. Antenatal ultrasound examination may be useful in identifying congenital intracranial tumours.
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ItemHealth services : knowledge, use and satisfaction of Afghan, Iranian and Iraqi settlers in Australia(Radcliffe Publishing, 2007)This paper reports the findings of a study examining the knowledge of, use of and satisfaction with local primary healthcare services reported by new arrivals to Australia from Iran, Iraq and Afghanistan. The study sample consisted of a purposive sample of 98 new settlers from the selected countries and used a semi-structured questionnaire and focus groups to attain information. Key findings were that friends and family were the greatest sources of health provider information and there was a lack of both more general health information and understanding of the health system. While study participants were able to access primary healthcare services and were generally satisfied, several major operational deficiencies were reported. General practitioners (GPs) were the major health providers for these groups. Health-seeking behaviours were strongly influenced by the country of birth in comparison with the other examined factors, and experiences of health service encounters also varied greatly between countries of birth. The facility’s proximity to the participant’s home was a strong influence in the selection of health services. The researchers recommend that a network of appropriately supported and staffed community health centres and/ or GP clinics is needed in areas where there are high concentrations of refugees and immigrants.
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ItemNo Preview AvailableHealth issues in newly arrived African refugees attending general practice clinics in Melbourne(WILEY, 2006-12-04)OBJECTIVE: To identify the most common health issues diagnosed by general practitioners in newly arrived African refugees. DESIGN: Descriptive study based on a purposive sample of six GPs to collate data from medical records of patients from African countries who had attended their clinics for the first time between 1 January and 30 June 2005. SETTING: Two community health centres and two private general practices in metropolitan Melbourne. PARTICIPANTS: African refugee patients who arrived in Australia after 1 June 2004 and were seen by the six participating GPs between 1 January and 30 June 2005. MAIN OUTCOME MEASURES: Demographic characteristics, laboratory test results and final diagnoses. RESULTS: Data were collected from 258 patient files. Most patients were from Sudan (57%) or Liberia (17%). Half were aged under 15 years. The most common health problems identified were inadequate vaccinations, nutritional deficiencies (vitamin D and iron), infectious diseases (gastrointestinal infections, schistosomiasis, and latent tuberculosis) and dental disease. Musculoskeletal, psychological and social problems were common in adults. 37% of patients were tested for latent tuberculosis, and 25% of these tested positive. CONCLUSIONS: African refugees require comprehensive health assessments for undiagnosed and untreated health problems. While most of the common diseases identified are non-communicable, if left untreated they will affect the long-term health and productivity of new settlers.
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ItemNo long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine(Elsevier, 2016-06)Background: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. Objective: This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Methods: Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Results: Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Conclusion: Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.
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ItemNo Preview AvailableFinancial sustainability planning for immunization services in Cambodia(OXFORD UNIV PRESS, 2006-07)The expanded programme of immunization was established in Cambodia in 1986. In 2002, 67% of eligible children were immunized, despite significant health sector and macro-economic financial constraints. A financial sustainability planning process for immunization was introduced in 2002, in order to mobilize national and international resources in support of the achievement of child health objectives. The aim of this paper is to outline this process, describe its early impact as an advocacy tool and recommend additional strategies for mobilizing additional resources for health. The methods of financial sustainability planning are described, including the advocacy strategies that were applied. Analysis of financial sustainability planning results indicates rising programme costs associated with new vaccine introduction and new technologies. Despite this, the national programme has demonstrated important early successes in using financial sustainability planning to advocate for increased mobilization of national and international sources of funding for immunization. The national immunization programme nevertheless faces formidable system and financial challenges in the coming years associated with rising costs, potentially diminishing sources of international assistance, and the developing role of sub-national authorities in programme management and financing.
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ItemNo Preview AvailableParasite-specific IgG response and peripheral blood eosinophil count following albendazole treatment for presumed chronic strongyloidiasis(OXFORD UNIV PRESS INC, 2006)BACKGROUND: In developed countries, asymptomatic chronic Strongyloides stercoralis infection occurs in immigrants from endemic regions of the world. Accurate and reliable means of diagnosis and follow-up are required for effective management. The role of S stercoralis enzyme-linked immunosorbent assay (ELISA) in this context was examined. METHODS: In this study, 95 asymptomatic Laotian immigrants living in Melbourne, Australia, for an average of 12 years, were screened for S stercoralis infection using stool microscopy, eosinophil count, and serology by ELISA. Twenty-two patients with a positive ELISA were treated with albendazole, 400 mg twice daily for 3 days, and monitored with serology, fecal microscopy, and eosinophil counts at 2, 6, 12, and 36 months after treatment. RESULTS: Patients with moderately reactive baseline ELISA and no eosinophilia had no significant change in either measure over the 36 months of follow-up. All patients with a strongly reactive baseline ELISA showed a reduction in reactivity over the first 6 months of treatment. However, in 50% of these patients, reactivity increased between 12 and 36 months, suggesting treatment failure and relapse of infection. One patient had confirmed treatment failure based on the development of hyperinfection syndrome. CONCLUSION: The results support evidence that serology is a valuable tool in monitoring treatment responses in patients with suspected strongyloidiasis and highlights the need to ensure that S stercoralis is completely eradicated after treatment.