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      Intradermal rabies pre-exposure vaccination schedules in older travellers: comparison of immunogenicity post-primary course and post-booster

      1 , 2 , 2 , 2 , 1 , 3
      Journal of Travel Medicine
      Oxford University Press (OUP)

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          Abstract

          Background

          Intradermal (ID) rabies vaccination for pre-exposure prophylaxis (PrEP) has become increasingly popular; however, there is limited evidence about the effectiveness of different ID PrEP schedules in travellers aged > 50 years or their response to ID boosters. This study aimed to compare across different ID vaccine schedules and age groups the proportion of travellers who were seropositive after (i) primary course of ID PrEP and (ii) a booster.

          Methods

          Travellers who received ID PrEP at a travel medicine clinic in South Australia from 2000 to 2016 were included. Three schedules were examined: 1IDx3 (1 × 0.1 ml on days 0, 7, 21–28), 2IDx2 (2 × 0.1 ml on days 0, 7) and 4IDx1 (4x0.1 ml on day 0). The 4IDx1 is a non-standard schedule that has been previously explored in research settings, but not endorsed by WHO for PrEP. Antibody titres of ≥0.5 IU/ml were considered seropositive. The proportion seropositive after a primary course or post-booster was estimated for each schedule and age category. Predictors of seronegative status after a primary course were examined using multivariable logistic regression models.

          Results

          Overall, 835 travellers (median age 37.5 years; 37.1% > 50 years) were included in the analyses of seropositivity after a primary course. Another group of 771 travellers (median age 45.9 years; 43.5% > 50 years) was included in the analyses of seropositivity post-booster. The proportion seropositive after primary course was 92.5% (95%CI: 90.5–94.1%) and highest with the 1IDx3 schedule (93.4%; 95%CI: 91.4–95.0%). After adjusting for age and timing of the serology, the odds of seronegative status were four times higher (OR 4.17; 95%CI: 1.43–12.18) with the 4IDx1 schedule compared to 1IDx3. Overall, 98.7% (95%CI: 97.6–99.3%) were seropositive post-booster. Of 46 travellers who received a booster ≥3 years after PrEP, all were seropositive post-booster.

          Conclusions

          In older travellers, the 1IDx3 schedule was the most effective, and a high proportion were seropositive post-booster even many years after a primary course.

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          Most cited references29

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          Estimating the Global Burden of Endemic Canine Rabies

          Background Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. Methodology/Principal Findings We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). Conclusions/Significance This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.
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            Immunosenescence: emerging challenges for an ageing population.

            It is now becoming apparent that the immune system undergoes age-associated alterations, which accumulate to produce a progressive deterioration in the ability to respond to infections and to develop immunity after vaccination, both of which are associated with a higher mortality rate in the elderly. Immunosenescence, defined as the changes in the immune system associated with age, has been gathering interest in the scientific and health-care sectors alike. The rise in its recognition is both pertinent and timely given the increasing average age and the corresponding failure to increase healthy life expectancy. This review attempts to highlight the age-dependent defects in the innate and adaptive immune systems. While discussing the mechanisms that contribute to immunosenescence, with emphasis on the extrinsic factors, particular attention will be focused on thymic involution. Finally, we illuminate potential therapies that could be employed to help us live a longer, fuller and healthier life.
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              Immunosenescence of ageing.

              Ageing is a complex process that negatively impacts the development of the immune system and its ability to function. The mechanisms that underlie these age-related defects are broad and range from defects in the haematopoietic bone marrow to defects in peripheral lymphocyte migration, maturation and function. The thymus is a central lymphoid organ responsible for production of naïve T cells, which play a vital role in mediating both cellular and humoral immunity. Chronic involution of the thymus gland is thought to be one of the major contributing factors to loss of immune function with increasing age. It has recently been demonstrated that thymic atrophy is mediated by a shift from a stimulatory to a suppressive cytokine microenvironment. In this review we present an overview of the morphological, cellular and biochemical changes that have been implicated in the decline of thymic and peripheral immune function with ageing. We conclude with the clinical implications of age-associated immunosenescence to vaccine development for tumours and infectious disease. A fundamental understanding of the complex mechanisms by which ageing attenuates immune function will enable translational research teams to develop new therapies and vaccines specifically aimed at overcoming these defects in immunological function in the aged. Copyright (c) 2007 Pathological Society of Great Britain and Ireland.
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                Author and article information

                Journal
                Journal of Travel Medicine
                Oxford University Press (OUP)
                1195-1982
                1708-8305
                October 2020
                November 09 2020
                January 14 2020
                October 2020
                November 09 2020
                January 14 2020
                : 27
                : 7
                Affiliations
                [1 ]Research School of Population Health, Australian National University, Canberra, Australia
                [2 ]Travel-Bug Vaccination Clinic, Adelaide, Australia
                [3 ]Dr Deb The Travel Doctor, Travel Medicine Alliance, Brisbane, Australia
                Article
                10.1093/jtm/taaa006
                31943042
                ec0b5ae8-eab3-417d-abdf-a65117d78346
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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