Status of HPV vaccine introduction and barriers to country uptake.

During the last 12 years, over 80 countries have introduced national HPV vaccination programs. The majority of these countries are high or upper-middle income countries. The barriers to HPV vaccine introduction remain greatest in those countries with the highest burden of cervical cancer and the most need for vaccination. Innovation and global leadership is required to increase and sustain introductions in low income and lower-middle income countries

The TeV Diffuse Cosmic Neutrino Spectrum and the Nature of Astrophysical Neutrino Sources

The diffuse flux of cosmic neutrinos has been measured by the IceCube Observatory from TeV to PeV energies. We show that an improved characterization of this flux at the lower energies, TeV and sub-TeV, reveals important information on the nature of the astrophysical neutrino sources in a model-independent way. Most significantly, it could confirm the present indications that neutrinos originate in cosmic environments that are optically thick to GeV-TeV $\gamma$-rays. This conclusion will become inevitable if a steeper or even uninterrupted neutrino power law is observed in the TeV region. In such $\gamma$-ray-obscured sources, the $\gamma$-rays that inevitably accompany cosmic neutrinos will cascade down to MeV-GeV energies. The requirement that the cascaded $\gamma$-ray flux accompanying cosmic neutrinos should not exceed the observed diffuse $\gamma$-ray background, puts constraints on the peak energy and density of the radiation fields in the sources. Our calculations inspired by the existing data suggest that a fraction of the observed diffuse MeV-GeV $\gamma$-ray background may be contributed by neutrino sources with intense radiation fields that obscure the high-energy $\gamma$-ray emission accompanying the neutrinos.Comment: 9 pages, 3 figure

Milky Way as a Neutrino Desert Revealed by IceCube Galactic Plane Observation

The Galactic diffuse emission (GDE) is formed when cosmic rays leave the sources where they were accelerated, diffusively propagate in the Galactic magnetic field, and interact with the interstellar medium and interstellar radiation field. GDE in $\gamma$-ray (GDE-$\gamma$) has been observed up to sub-PeV energies, though its origin may be explained by either cosmic-ray nuclei or electrons. We show that the $\gamma$-rays accompanying the high-energy neutrinos recently observed by the IceCube Observatory from the Galactic plane have a flux that is consistent with the GDE-$\gamma$ observed by the {\it Fermi}-LAT and Tibet AS$\gamma$ experiments around 1 TeV and 0.5 PeV, respectively. The consistency suggests that the diffuse $\gamma$-ray emission above $\sim$1TeV could be dominated by hadronuclear interactions, though partial leptonic contribution cannot be excluded. Moreover, by comparing the fluxes of the Galactic and extragalactic diffuse emission backgrounds, we find that the neutrino luminosity of the Milky Way is one to two orders of magnitude lower than the average of distant galaxies. This implies that our Galaxy has not hosted the type of neutrino emitters that dominates the isotropic neutrino background at least in the past few tens of kiloyears.Comment: 20 pages, 2 figures + Supplemental Material. Accepted for publication in Nature Astronom

Evaluating human papillomavirus vaccine introduction in Tanzania and other low-resource settings.

Evaluation of the success and impact of human papillomavirus (HPV) vaccine introduction and collation of key lessons learnt in low and middle-income countries (LAMICs) is now possible given the number of recent HPV vaccine pilots, or ‘demonstration projects’, and national programmes. Results may be useful for countries that have not yet commenced implementation of the HPV vaccine and may also be generalizable to future introductions of other pre-adolescent and adolescent vaccines. This PhD addresses four aspects of HPV vaccine introduction: 1) barriers to adherence to multi-dose vaccine schedules, 2) the potential impact of the HPV vaccine on human immunodeficiency virus (HIV) acquisition, 3) the potential impact of HPV vaccine introduction on other health services, and 4) lessons learnt and recommendations for HPV vaccine implementation in LAMICs. A systematic review of the published literature on factors influencing multi-dose vaccine adherence in adolescents was conducted. The paucity of published data from LAMICs meant that no geographical restriction was set in the search terms. The majority of research included in the synthesis originated in the United States of America (USA), where race, insurance status and parental healthcare seeking behaviour were found to be predictors of vaccine schedule completion. As vaccination programmes in older children become more established in LAMICs, more research is needed on factors influencing adherence in these settings. The association between HPV infection and subsequent HIV acquisition was assessed in a nested case-control study using stored cervical samples from previous study cohorts of Tanzanian and Ugandan women. In contrast to previous observational studies that have found an association between HPV infection and HIV acquisition in men and women, we found no evidence of an association between HPV infection, clearance or persistence, and subsequent HIV acquisition. This precluded the calculation of an estimate of the potential population attributable fraction for the effect of HPV infection (and vaccination) on HIV incidence. Data from health facility register books and interviews with health workers in two regions of Tanzania were analysed to examine the potential impact of HPV vaccination introduction through a demonstration project in Northern Tanzania in 2014 on the provision of routine primary health services. A controlled before-after analysis was carried out on count data of consultations at facilities involved in HPV vaccine delivery in Kilimanjaro Region, and control facilities in a neighbouring region. Interviews with health workers provided important contextual information. There was no evidence that the number of consultations at the health facilities fell during campaign weeks in intervention facilities compared to control facilities. Utilisation of the health facilities was highly variable. Interviews indicated that the quality of care provided at the facility during vaccination campaigns might be affected by staff absence. Lessons learnt from 37 LAMICs with at least one year of experience in HPV vaccine delivery were collated from 41 published articles, 124 pieces of unpublished literature, and 27 key informant interviews. Recommendations were formulated in 7 key themes: preparation, communication, delivery, coverage achievements, sustainability, value of demonstration projects and common pitfalls. Lessons were consistent across world regions and included the importance of collaboration during planning between the ministries of health and education, strategies to respond to rumours and challenges encountered during delivery. Key findings were disseminated widely and stimulated on-going supplemental research. There is now a large evidence base to support the rationale for HPV vaccine introduction and its successful delivery in LAMICs, which currently suffer the heaviest burden of cervical cancer disease in the world. To date, HPV vaccine delivery in low resource settings has achieved high coverage and experienced fewer barriers than expected. It is clear that if funding is available, LAMICs can effectively introduce the HPV vaccine nationally and prevent a high burden of a major and serious disease in women

High-energy Neutrinos from the Inner Circumnuclear Region of NGC 1068

High-energy neutrinos are detected by the IceCube Observatory in the direction of NGC 1068, the archetypical type II Seyfert galaxy. The neutrino flux, surprisingly, is more than an order of magnitude higher than the $\gamma$-ray upper limits at measured TeV energy, posing tight constraints on the physical conditions of a neutrino production site. We report an analysis of the sub-millimeter, mid-infrared, and ultraviolet observations of the central $50$ pc of NGC 1068 and suggest that the inner dusty torus and the region where the jet interacts with the surrounding interstellar medium (ISM) may be a potential neutrino production site. Based on radiation and magnetic field properties derived from observations, we calculate the electromagnetic cascade of the $\gamma$-rays accompanying the neutrinos. Our model may explain the observed neutrino flux above $\sim 10$ TeV and contribute to 20% of the neutrino flux at 3 TeV. It predicts a unique sub-TeV $\gamma$-ray component, which could be identified by a future observation. Jet-ISM interactions are commonly observed in the proximity of jets of both supermassive and stellar-mass black holes. Our results imply that such interaction regions could be $\gamma$-ray obscured neutrino production sites, which are needed to explain the IceCube diffuse neutrino flux.Comment: 8 pages, 4 figures, 1 tabl

Pneumococcal conjugate vaccine dose-ranging studies in humans: A systematic review

Background: Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity. Methods: A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule. Results: We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses. Conclusion: For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose–response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use

Pattern analysis of vegan eating reveals healthy and unhealthy patterns within the vegan diet

Objective: This study aimed to identify the types of foods that constitute a vegan diet and establish patterns within the diet. Dietary pattern analysis, a key instrument for exploring the correlation between health and disease was used to identify patterns within the vegan diet. Design: A modified version of the EPIC-Norfolk food frequency questionnaire (FFQ) was created and validated to include vegan foods and launched on social media. Setting: UK participants, recruited online Participants: A convenience sample of 129 vegans voluntarily completed the FFQ. Collected data was converted to reflect weekly consumption to enable factor and cluster analyses. Results: Factor analysis identified four distinct dietary patterns including: 1) convenience, (22%); 2) health conscious, (12%); 3) unhealthy, (9%); and 4) traditional vegan (7%). Whilst two healthy patterns were defined, the convenience pattern was the most identifiable pattern with a prominence of vegan convenience meals and snacks, vegan sweets and desserts, sauces, condiments and fats. Cluster analysis identified three clusters, cluster one ‘convenience’ (26.8%), cluster two, ‘traditional’ (22%) and cluster 3 ‘health conscious’ (51.2%). Clusters one and two consisted of an array of ultra-processed vegan food items. Together, both clusters represent almost half of participants and yielding similar results to the predominant dietary pattern, strengthens the factor analysis. Conclusions: These novel results highlight a need for further dietary pattern studies with full nutrition and blood metabolite analysis in larger samples of vegans to enhance and ratify these results

Factors influencing completion of multi-dose vaccine schedules in adolescents: a systematic review.

BACKGROUND: Completion of multiple dose vaccine schedules is crucial to ensure a protective immune response, and maximise vaccine cost-effectiveness. While barriers and facilitators to vaccine uptake have recently been reviewed, there is no comprehensive review of factors influencing subsequent adherence or completion, which is key to achieving vaccine effectiveness. This study identifies and summarises the literature on factors affecting completion of multi-dose vaccine schedules by adolescents. METHODS: Ten online databases and four websites were searched (February 2014). Studies with analysis of factors predicting completion of multi-dose vaccines were included. Study participants within 9-19 years of age were included in the review. The defined outcome was completion of the vaccine series within 1 year among those who received the first dose. RESULTS: Overall, 6159 abstracts were screened, and 502 full texts were reviewed. Sixty one studies were eligible for this review. All except two were set in high-income countries. Included studies evaluated human papillomavirus vaccine, hepatitis A, hepatitis B, and varicella vaccines. Reported vaccine completion rates, among those who initiated vaccination, ranged from 27% to over 90%. Minority racial or ethnic groups and inadequate health insurance coverage were risk factors for low completion, irrespective of initiation rates. Parental healthcare seeking behaviour was positively associated with completion. Vaccine delivery in schools was associated with higher completion than delivery in the community or health facilities. Gender, prior healthcare use and socio-economic status rarely remained significant risks or protective factors in multivariate analysis. CONCLUSIONS: Almost all studies investigating factors affecting completion have been carried out in developed countries and investigate a limited range of variables. Increased understanding of barriers to completion in adolescents will be invaluable to future new vaccine introductions and the further development of an adolescent health platform. PROSPERO reg# CRD42014006765

The value of demonstration projects for new interventions: The case of human papillomavirus vaccine introduction in low- and middle-income countries.

Demonstration projects or pilots of new public health interventions aim to build learning and capacity to inform country-wide implementation. Authors examined the value of HPV vaccination demonstration projects and initial national programmes in low-income and lower-middle-income countries, including potential drawbacks and how value for national scale-up might be increased. Data from a systematic review and key informant interviews, analyzed thematically, included 55 demonstration projects and 8 national programmes implemented between 2007-2015 (89 years' experience). Initial demonstration projects quickly provided consistent lessons. Value would increase if projects were designed to inform sustainable national scale-up. Well-designed projects can test multiple delivery strategies, implementation for challenging areas and populations, and integration with national systems. Introduction of vaccines or other health interventions, particularly those involving new target groups or delivery strategies, needs flexible funding approaches to address specific questions of scalability and sustainability, including learning lessons through phased national expansion