Sustained Decline in Hospitalisations for Anogenital Warts in Australia: Analysis of National Hospital Morbidity Data 2003-2020.

In Australia, school-based human papillomavirus (HPV) vaccination was introduced initially for girls in 2007, and then also for boys in 2013. While studies have shown declines in the incidence of anogenital warts, there is a paucity of recent data analysis assessing the impact of vaccination on more severe disease. The National Hospital Morbidity Database of the Australian Institute of Health and Welfare (AIHW) hospitalisation admission data that included ICD-10-AM code A63.0 ('anogenital warts') as the diagnoses, for the years 2003-2020, were analysed to estimate hospitalisation rates per 100,000 mid-year population. The annual average hospitalisation rates per 100,000 population for anogenital warts in both genders combined in the age groups 10-19 years, 20-29 years, and 30-39 years decreased, respectively, from 16.9, 49.6, and 23.6 in 2003-2007 (pre-vaccine period) to 2.6, 15.2, and 14.6 in 2008-2020 (post-vaccine period), equating to declines of 84.7%, 69.4%, and 38.2%, respectively. Following the introduction of the boy's vaccination, hospitalisation rates decreased further in the respective age bands from 4.3, 22.8, and 18.4 in 2008-2013 (early post-vaccine period) to 1.1, 9.3, and 11.7 in 2014-2020 (late post-vaccine period), equating to respective declines of 73.4%, 59.3%, and 36.4%. This analysis confirms that there is a substantial incremental decline in anogenital warts hospitalisations among Australians aged 10-39 years.

Annual immunisation coverage report 2021.

Introduction: We analysed Australian Immunisation Register (AIR) data as at 3 April 2022 for children, adolescents and adults for the calendar year 2021, with data on trends from previous years also presented. Children: 'Fully vaccinated' coverage in Australian children in 2021 was 0.6-0.8 of a percentage point lower than in 2020 at the 12-month (94.2%) and 60-month (94.0%) age assessment milestones, but stable at the 24-month milestone (92.1%). Due to the lag time involved in assessment at milestone ages, 'fully vaccinated' coverage figures for 2020 and 2021 predominantly reflect vaccinations due in 2019 and 2020, respectively, and hence show a small impact on childhood coverage in the first year of the coronavirus disease 2019 (COVID-19) pandemic. 'Fully vaccinated' coverage in Aboriginal and Torres Strait Islander (hereafter respectfully referred to as Indigenous) children was 0.7-1.5 percentage points lower in 2021 than 2020 at the 12-month (91.6%), 24-month (90.1%) and 60-month (96.3%) milestones, although 2.3 percentage points higher than children overall at 60 months. Influenza vaccination coverage in children aged 6-59 months was approximately 20 percentage points lower in 2021 than 2020, both for children overall (26.5%) and for Indigenous children (22.5%). 'On time' vaccination (within 30 days of the recommended age) was up to two percentage points lower in 2021 than 2020 for vaccines due at 4 and 6 months of age, suggesting possible pandemic impacts, but was similar or higher for vaccines due at 12 months of age. While on-time vaccination in Indigenous children has improved progressively since 2012, it remained 6-13 percentage points lower than in children overall in 2021. 'Fully vaccinated' coverage at the earlier milestones (3 months after due date of last scheduled vaccine) of 9, 15, 21 and 51 months was 1.5-2.8 percentage points lower for children living in the least advantaged residential area quintile than the most advantaged, a similar disparity as in 2020. Coverage at the earlier milestones was 2.3-10.0 percentage points lower for Indigenous children living in remote areas than in major cities and regional areas, with disparity at 21 months of age 2.1-2.2 percentage points higher in 2021 than in 2020, and 1.2-2.1 percentage points higher at 51 months. Adolescents: In 2021, a total of 80.3% of girls and 77.2% of boys (and 73.3% and 66.2% of Indigenous girls and boys) had completed the human papillomavirus (HPV) vaccination schedule by 15 years of age, 0.2-0.4 of a percentage point lower than 2020 (1.7-1.8 percentage points for Indigenous), reflecting vaccinations due in school programs prior to the pandemic with possible pandemic impact on catch-up vaccination. However, the proportion of adolescents completing the two-dose HPV vaccination schedule within a calendar year was 15.3 percentage points lower in 2021 than 2020 and 26.9 percentage points lower than in 2019, likely due to pandemic-related disruption to school-based programs. Additionally, 87.3% of adolescents (83.8% for Indigenous) had received the recommended booster dose of diphtheria-tetanus-acellular pertussis (dTpa) vaccine by 15 years, and 76.1% (66.7% for Indigenous) the recommended meningococcal ACWY vaccine dose by 17 years of age. Adults: Zoster vaccine coverage in 2021 remained relatively low, at just over 30%, in adults aged 70 years, but increased to 47% in those aged 71-79 years, reflecting ongoing catch-up vaccination. Coverage of 13vPCV was low in 2021, reaching 17.2% in adults aged 70 years and 20.1% in those aged 71-79 years. Influenza vaccination coverage in adults in 2021 was progressively higher with increasing age, reaching 62.1% in the 65-74 years age group (64.6% in Indigenous) and 68.5% in the 75+ years age group (67.7% in Indigenous). Influenza vaccine coverage for other National Immunisation Program (NIP)-eligible Indigenous adult age groups was only 22.0% for those aged 20-49 years, and 43.5% for those aged 50-64 years. By the end of 2021, a total of 91.6% of people in Australia aged 16+ years had received a second dose of a COVID-19 vaccine (71.8% for Indigenous), with over 99% of those aged 70+ years having received a second dose. Conclusions: Vaccination coverage in children and adolescents remained relatively high in 2021, although with some evidence of COVID-19 pandemic impacts, particularly on receipt of two doses of HPV vaccine within the same calendar year. It will be important to ensure catch-up vaccination in children and adolescents occurs. A strengthened focus on adult vaccination is needed, as coverage remained suboptimal in 2021. The impact of mandatory reporting of all NIP vaccinations from mid-2021, on completeness of AIR data, has not yet been formally evaluated.

Tumor lysis syndrome in premature infant prompting early resection of a large sacrococcygeal teratoma: a case report.

BACKGROUND: Sacrococcygeal teratomas (SCTs) are the most common congenital neoplasm and often require resection soon after birth. There are rare reports of cardiac arrest during surgery due to manipulation of the tumor triggering secondary necrosis and hyperkalemia. CASE PRESENTATION: This case describes a very preterm infant with a SCT who develops spontaneous preoperative tumor lysis syndrome (TLS). The medical team utilized rasburicase and the patient underwent total gross resection at 40 h of life. CONCLUSIONS: We emphasize the importance of the early recognition and management of tumor lysis syndrome in SCT with rasburicase, aggressive management of hyperkalemia and consideration of early resection of SCTs even in the case of a very premature infant.

Stakeholder Perspectives of Australia's National HPV Vaccination Program.

Australia has been a world leader in human papillomavirus (HPV) vaccination and was the first country to implement a fully funded national HPV vaccination program, from 2007 for girls and 2013 for boys. In 2018 the program changed from a 4-valent to 9-valent HPV vaccine and a 3-dose to 2-dose standard schedule. We assessed stakeholder perspectives on factors influencing program outcomes and impact as part of a comprehensive program evaluation. In late 2019 and early 2020, we conducted 26 interviews with 42 key stakeholder participants and received 1513 survey responses from stakeholders including general practice staff and school-based nurse immunisers. Findings included that the 2-dose schedule is better accepted by schools and students and has reduced program cost and resource requirements. However, course completion rates have not increased as much as anticipated due to the 6-12 month dosing interval and reduced opportunities for school-based catch-up vaccination. Major reported barriers to increased vaccine coverage were absenteeism and consent form return. Vaccine hesitancy is not currently a major issue but remains a potential threat to the program. While Australia's HPV vaccination program is perceived as highly successful, measures to further enhance the program's impact and mitigate potential threats are important.

Surveillance of adverse events following immunisation in Australia annual report, 2020.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.

HPV vaccination coverage: slightly improved two-dose schedule completion estimates and historical estimates lower on AIR than HPV Register.

OBJECTIVE: To compare Australian Immunisation Register (AIR) human papillomavirus (HPV) vaccination coverage against historical data from the former National HPV Vaccination Program Register and estimate two-dose vaccination coverage. METHODS: Cross-sectional analysis of registry data for adolescent birth cohorts (1998-2007). Denominator populations were Medicare enrolments (AIR) and ABS estimated resident populations (HPV register). RESULTS: For adolescents aged <17 years, AIR coverage estimates were several percentage points lower than HPV register estimates due to a larger Medicare enrolment denominator. Completed course coverage (two or three valid doses) for 15-year-old females in 2020 was 81.5% and for males 78.6%, higher than completed course coverage in 15-year-olds in 2019 (79.7 and 76.8% respectively). First dose coverage was similar for Indigenous adolescents but course completion was lower, although improving over time. Course completion was slightly lower (3.5-5.7%) in areas of lowest socioeconomic status and greatest remoteness. CONCLUSIONS: Coverage is slightly lower using AIR than HPV register estimates. Moving from three to two doses has slightly improved completion, likely due to the wider dose spacing, but equity gaps remain. IMPLICATIONS FOR PUBLIC HEALTH: An ongoing focus on equity in vaccine delivery is needed. Systems, reminders and catch-up opportunities to ensure course completion remain important.

Antibiofilm and anticancer activities of unripe and ripe Azadirachta indica (neem) seed extracts.

BACKGROUND: Antibiotic resistances of pathogens and breast cancer warrant the search for new alternative strategies. Phytoextracts can eradicate microbe-borne diseases as well as cancer with lower side effects compared to conventional antibiotics. AIM: Unripe and ripe Azadirachta indica (neem) seed extracts were explored as potential antibiofilm and anticancer agents in combating multidrug-resistant infectious bacteria as well as anticancer agents against the MDR breast cancer cell lines. METHODS: Shed-dried neem seeds (both unripe and ripe) were pulverized and extracted using methanol. The chemical components were identified with FTIR and gas chromatography - mass spectrometry. Antibiofilm activity of neem seed extracts were assessed in terms of minimum biofilm inhibitory concentration (MBIC), minimum biofilm eradication concentration (MBEC), and fluorescence microscopic studies on Staphylococcus aureus and Vibrio cholerae. Bacterial cells were studied by fluorescence microscopy using acridine orange/ethidium bromide as the staining agents. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were evaluated to observe the antibacterial activities. Cytotoxicity of the extracts against human blood lymphocytes and the anticancer activity against drug-resistant breast cancer cell lines were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and fluorescence-activated cell sorting (FACS) studies. RESULTS: 4-Ethyl-2-hydroxy-2-cyclopentene-1-one, phthalic acid, and 2-hexyl-tetrahydro thiophane were the major compounds in unripe neem seed, whereas 3,5-dihydroxy-6-methyl-2,3-dihydro-4-H-pyran-4-one and 4-ethylbenzamide were predominant in ripe neem seed. Triazine derivatives were also common for both the extracts. MBIC values of unripe and ripe neem seed extracts for S. aureus are 75 and 100 µg/mL, respectively, and for V. cholerae, they are 100 and 300 µg/mL, respectively. MBEC values of unripe and ripe seed extracts are 500 and 300 µg/mL, respectively for S. aureus and for V. cholerae the values are 700 and 500 µg/mL, respectively. Fluorescence microscopic studies at 16 and 24 h, after bacterial culture, demonstrate enhanced antibiofilm activity for the ripe seed extract than that of the unripe seeds for both the bacteria. MTT assay reveals lower cytotoxicity of both the extracts towards normal blood lymphocytes, and anticancer activity against breast cancer cell line (MDA-MB-231) with superior activity of ripe seed extract. FACS studies further supported higher anticancer activity for ripe seed extract. CONCLUSIONS: Methanolic extract of neem seeds could substantially inhibit and eradicate biofilm along with their potent antibacterial and anticancer activities. Both the extracts showed higher antibiofilm and antibacterial activity against S. aureus (gram-positive) than V. cholerae (gram-negative). Moreover, ripe seed extract showed higher antibiofilm and anticancer activity than unripe extracts.

Surveillance of adverse events following immunisation in Australia annual report, 2019.

ABSTRACT: This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2019 reported to the Therapeutic Goods Administration (TGA) and describes reporting trends over the 20-year period from 1 January 2000 to 31 December 2019. There were 3,782 AEFI records for vaccines administered in 2019, an annual AEFI reporting rate of 14.9 per 100,000 population. There was an 11.8% decrease in the overall AEFI reporting rate in 2019 compared to 2018 (16.9 per 100,000 population). This decrease in the AEFI reporting rate in 2019 was mainly attributable to a decline in reported adverse events related to the human papillomavirus (HPV), dTpa, meningococcal ACWY and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2019 were similar to 2018. The most commonly-reported adverse events were injection site reaction (35.8%), rash (16.6%), pyrexia (15.3%), vomiting (8.1%), urticaria (5.8%), pain (5.8%) and headache (5.7%). There were five deaths reported to the TGA. In one report, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining four reports, no clear causal relationship with vaccination was found.

Adverse events following HPV vaccination: 11 years of surveillance in Australia.

BACKGROUND: Australia was the first country to implement a fully funded vaccination program with quadrivalent human papillomavirus vaccine (4vHPV) in 2007, including males from 2013. We examined adverse events (AE) following vaccination with 4vHPV from 11 years of post-marketing data, focusing on a period of enhanced surveillance and adverse events of special interest (AESI). METHODS: AE following 4vHPV doses administered between April 2007 and December 2017 reported to Australia's national regulator, the Therapeutic Goods Administration, were examined; reports collected during enhanced surveillance in 2013 and 2014 were analyzed separately. Age and sex-specific rates, using denominator data from the national HPV vaccination register, were determined. Pre-specified AESI were identified using Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms and examined in detail. FINDINGS: Following nine million doses of 4vHPV vaccine administered in Australia, 4551 AE reports were identified. The crude reporting rate was 39.8 per 100 000 doses in the funded cohorts, excluding the enhanced surveillance period. The reported rate of syncope in 12 to 13-year-old males and females was 29.6 per 100 000 doses during enhanced surveillance and 7.1 per 100 000 doses during the remaining study period; rates of syncope were higher in younger compared to older adolescents. The rate of anaphylaxis (0.32 per 100 000 doses) was consistent with published rates. Other AESI including autoimmune disease, postural orthostatic tachycardia syndrome, primary ovarian insufficiency, Guillain-Barré syndrome, complex regional pain syndrome and venous thromboembolism, were reported at low rates and analysis did not reveal unexpected patterns that would suggest causal association. INTERPRETATION: AESI, apart from syncope, were reported rarely. The higher rate of syncope among younger adolescents highlights the need for management protocols to prevent syncope-related injury. Analysis of this large, longitudinal dataset in a country with high vaccine uptake, including a period of enhanced surveillance, affirms the safety profile of 4vHPV.

Self assembled arjunolic acid acts as a smart weapon against cancer through TNF- α mediated ROS generation.

Arjunolic acid (AA) a plant derived pentacyclic triterpenoid which showed effective anticancer activity against MCF-7 and HeLa cells as well as no significant toxic effect was observed against normal lymphocytes. In the current study the self assemble property of arjunolic acid gives an extra emphasis on anticancer activity which was proved by several fluorescence studies like ROS generation, EtBr/AO and DAPI staining. At a selected dose of 50µg/ml AA disrupt the redox balance inside the cancer cells by producing reactive oxygen species. The apoptotic event was mediated by two key regulator proteins TNF-α and NF-κß which was proved here. The increment of the pro-inflammatory cytokines indicates the ROS mediated pathway of cancer cell apoptosis.

Type 1 Interferon Responses Underlie Tumor-Selective Replication of Oncolytic Measles Virus.

The mechanism of tumor-selective replication of oncolytic measles virus (MV) is poorly understood. Using a stepwise model of cellular transformation, in which oncogenic hits were additively expressed in human bone marrow-derived mesenchymal stromal cells, we show that MV-induced oncolysis increased progressively with transformation. The type 1 interferon (IFN) response to MV infection was significantly reduced and delayed, in accordance with the level of transformation. Consistently, we observed delayed and reduced signal transducer and activator of transcription (STAT1) phosphorylation in the fully transformed cells. Pre-treatment with IFNß restored resistance to MV-mediated oncolysis. Gene expression profiling to identify the genetic correlates of susceptibility to MV oncolysis revealed a dampened basal level of immune-related genes in the fully transformed cells compared to their normal counterparts. IFN-induced transmembrane protein 1 (IFITM1) was the foremost basally downregulated immune gene. Stable IFITM1 overexpression in MV-susceptible cells resulted in a 50% increase in cell viability and a significant reduction in viral replication at 24 h after MV infection. Overall, our data indicate that the basal reduction in functions of the type 1 IFN pathway is a major contributor to the oncolytic selectivity of MV. In particular, we have identified IFITM1 as a restriction factor for oncolytic MV, acting at early stages of infection.

Immunostimulatory effect of chitosan conjugated green copper oxide nanoparticles in tumor immunotherapy.

Current study demonstrates the immunogenic role of biopolymer coated green synthesized copper oxide nanoparticles by the induction of cellular immunity through the activation immune cells. Alongside humoral immunity response was triggered by the surface coated NPs through IgG response which indicate the adjuvanic role of the nano conjugate. Th1 (Type 1 and Type 2 helper T cells) and Th2 cells were activated after the treatment with nano conjugate and act as an immunostimulant which would inhibit the proliferation of breast cancer (MCF-7) and cervical cancer (HeLa) cells in in vitro. Solid tumor induced by 4 T1 cells were also inhibited in in vivo Balb/C mice model. Secretion of pro-inflammatory cytokines and the increase in CD + 4 populations indicate the activation of immune cells in the current study. Immunotherapy by the help of metal nano conjugate can be an effective tool to eradicate the cancer cells from the system.

Annual Immunisation Coverage Report 2017.

This eleventh national annual immunisation coverage report focuses on data for the calendar year 2017 derived from the Australian Immunisation Register (AIR) and the National Human Papillomavirus (HPV) Vaccination Program Register. This is the first report to include data on HPV vaccine course completion in Aboriginal and Torres Strait Islander (Indigenous) adolescents. 'Fully immunised' vaccination coverage in 2017 increased at the 12-month assessment age reaching 93.8% in December 2017, and at the 60-month assessment age reaching 94.5%. 'Fully immunised' coverage at the 24-month assessment age decreased slightly to 89.8% in December 2017, following amendment in December 2016 to require the fourth DTPa vaccine dose at 18 months. 'Fully immunised' coverage at 12 and 60 months of age in Indigenous children reached the highest ever recorded levels of 93.2% and 96.9% in December 2017. Catch-up vaccination activity for the second dose of measles-mumps-rubella-containing vaccine was considerably higher in 2017 for Indigenous compared to non-Indigenous adolescents aged 10-19 years (20.3% vs. 6.4%, respectively, of those who had not previously received that dose). In 2017, 80.2% of females and 75.9% of males aged 15 years had received a full course of three doses of human papillomavirus (HPV) vaccine. Of those who received dose one, 79% and 77% respectively of Indigenous girls and boys aged 15 years in 2017 completed three doses, compared to 91% and 90% of non-Indigenous girls and boys, respectively. A separate future report is planned to present adult AIR data and to assess completeness of reporting.

Annual Immunisation Coverage Report 2016.

This tenth annual immunisation coverage report shows data for the calendar year 2016 derived from the Australian Immunisation Register (AIR) and the National Human Papillomavirus (HPV) Vaccination Program Register. After a decade of being largely stable at around 90%, 'fully immunised' coverage at the 12-month assessment age increased in 2016 to reach 93.7% for the age assessment quarterly data point in December 2016, similar to the 93.4% for the age assessment quarterly data point in December 2016 for 60 months of age. Implementation of the 'No Jab No Pay' policy may have contributed to these increases. While 'fully immunised' coverage at the 24-month age assessment milestone decreased marginally from 90.8%, in December 2015, to 89.6% for the age assessment quarterly data point in December 2016, this was likely due to the assessment algorithm being amended in December 2016 to include four doses of DTPa vaccine instead of three, following reintroduction of the 18-month booster dose. Among Indigenous children, the gap in coverage assessed at 12 months of age decreased fourfold, from 6.7 percentage points in March 2013 to only 1.7 percentage points lower than non-Indigenous children in December 2016. Since late 2012, 'fully immunised' coverage among Indigenous children at 60 months of age has been higher than for non-Indigenous children. Vaccine coverage for the nationally funded seasonal influenza vaccine program for Indigenous children aged 6 months to <5 years, which commenced in 2015, remained suboptimal nationally in 2016 at 11.6%. Changes in MMR coverage in adolescents were evaluated for the first time. Of the 411,157 ten- to nineteen-year-olds who were not recorded as receiving a second dose of MMR vaccine by 31 December 2015, 43,103 (10.5%) of them had received it by the end of 2016. Many of these catch-up doses are likely to have been administered as a result of the introduction on 1 January 2016 of the Australian Government's 'No Jab No Pay' policy. In 2016, 78.6% of girls aged 15 years had three documented doses of HPV vaccine (jurisdictional range 67.8-82.9%), whereas 72.9% of boys (up from 67.1 % in 2015) had received three doses.

Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress.

We investigated and modeled the mesenchymal stromal cell (MSC) niche in adult acute lymphoblastic leukemia (ALL). We used gene expression profiling, cytokine/chemokine quantification, flow cytometry, and a variety of imaging techniques to show that MSCs, directly isolated from the primary bone marrow specimens of patients with ALL, frequently adopted an activated, cancer-associated fibroblast phenotype. Normal, primary human MSCs and the MSC cell line HS27a both were activated de novo, when exposed to the reactive oxygen species (ROS)-inducing chemotherapy agents cytarabine (AraC) and daunorubicin (DNR), a phenomenon blocked by the antioxidant N-acetyl cysteine. Chemotherapy-activated HS27a cells were functionally evaluated in a coculture model with ALL targets. Activated MSCs prevented therapy-induced apoptosis and death in ALL targets, via mitochondrial transfer through tunneling nanotubes (TNTs). Reduction of mitochondrial transfer by selective mitochondrial depletion or interference with TNT formation by microtubule inhibitors, such as vincristine (VCR), prevented the "rescue" function of activated MSCs. Corticosteroids, also a mainstay of ALL therapy, prevented the activation of MSCs. We also demonstrated that AraC (but not VCR) induced activation of MSCs, mitochondrial transfer, and mitochondrial mass increase in a murine NSG model of disseminated SEM cell-derived ALL, wherein CD19+ cells closely associated with nestin+ MSCs after AraC, but not in the other conditions. Our data propose a readily clinically exploitable mechanism for improving treatment of ALL, in which traditional ROS-inducing chemotherapies are often ineffective at eradicating residual disease, despite efficiently killing the bulk population.

HPV vaccine coverage in Australia and associations with HPV vaccine information exposure among Australian Twitter users.

Introduction: Human papillomavirus (HPV) vaccine coverage in Australia is 80% for females and 76% for males. Attitudes may influence coverage but surveys measuring attitudes are resource-intensive. The aim of this study was to determine whether Twitter-derived estimates of HPV vaccine information exposure were associated with differences in coverage across regions in Australia. Methods: Regional differences in information exposure were estimated from 1,103,448 Australian Twitter users and 655,690 HPV vaccine related tweets posted between 6 September 2013 and 1 September 2017. Tweets about HPV vaccines were grouped using topic modelling; an algorithm for clustering text-based data. Proportional exposure to topics across 25 regions in Australia were used as factors to model HPV vaccine coverage in females and males, and compared to models using employment and education as factors. Results: Models using topic exposure measures were more closely correlated with HPV vaccine coverage (female: Pearson's R = 0.75 [0.49 to 0.88]; male: R = 0.76 [0.51 to 0.89]) than models using employment and education as factors (female: 0.39 [-0.02 to 0.68]; male: 0.36 [-0.04 to 0.66]). In Australia, positively-framed news tended to reach more Twitter users overall, but vaccine-critical information made up higher proportions of exposures among Twitter users in low coverage regions, where distorted characterisations of safety research and vaccine-critical blogs were popular. Conclusions: Twitter-derived models of information exposure were correlated with HPV vaccine coverage in Australia. Topic exposure measures may be useful for providing timely and localised reports of the information people access and share to inform the design of targeted vaccine promotion interventions.

Immunisation coverage annual report, 2015

This 9th annual immunisation coverage report shows data for 2015 derived from the Australian Childhood Immunisation Register and the National Human Papillomavirus (HPV) Vaccination Program Register. This report includes coverage data for 'fully immunised' and by individual vaccines at standard age milestones and timeliness of receipt at earlier ages according to Indigenous status. Overall, 'fully immunised' coverage has been mostly stable at the 12- and 24-month age milestones since late 2003, but at 60 months of age, coverage reached its highest ever level of 93% during 2015. As in previous years, coverage for 'fully immunised' at 12 and 24 months of age among Indigenous children was 3.4% and 3.3% lower than for non-Indigenous children overall, respectively. In 2015, 77.8% of Australian females aged 15 years had 3 documented doses of HPV vaccine (jurisdictional range 68.0­85.6%), and 86.2% had at least one dose, compared to 73.4% and 82.7%, respectively, in 2014. The differential of on-time vaccination between Indigenous and non-Indigenous children in 2015 diminished progressively from 18.4% for vaccines due at 12 months to 15.7% for those due at 24 months of age. In 2015, the proportion of children whose parents had registered an objection to vaccination was 1.2% at the national level, with large regional variations. This was a marked decrease from 1.8% in 2014 and the lowest rate of registered vaccination objection nationally since 2007 when it was 1.1%. Medical contraindication exemptions for Australia were more than double in 2015 compared with the previous year (635 to 1,401).

Preclinical Development of a Bispecific Antibody that Safely and Effectively Targets CD19 and CD47 for the Treatment of B-Cell Lymphoma and Leukemia.

CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to coengage CD47 and CD19 selectively on B cells. NI-1701 demonstrates favorable elimination kinetics with no deleterious effects seen on hematologic parameters following single or multiple administrations to nonhuman primates. Potent in vitro and in vivo activity is induced by NI-1701 to kill cancer cells across a plethora of B-cell malignancies and control tumor growth in xenograft mouse models. The mechanism affording maximal tumor growth inhibition by NI-1701 is dependent on the coengagement of CD47/CD19 on B cells inducing potent antibody-dependent cellular phagocytosis of the targeted cells. NI-1701-induced control of tumor growth in immunodeficient NOD/SCID mice was more effective than that achieved with the anti-CD20 targeted antibody, rituximab. Interestingly, a synergistic effect was seen when tumor-implanted mice were coadministered NI-1701 and rituximab leading to significantly improved tumor growth inhibition and regression in some animals. We describe herein, a novel bispecific antibody approach aimed at sensitizing B cells to become more readily phagocytosed and eliminated thus offering an alternative or adjunct therapeutic option to patients with B-cell malignancies refractory/resistant to anti-CD20-targeted therapy. Mol Cancer Ther; 17(8); 1739-51. ©2018 AACR.

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity.

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated.