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The case fatality rate of rabies, nearly 100%, is one of the most unique characteristic of this ancient virus infection. The crucial role rabies virus neutralizing antibody plays in protection is both well established and explanation of why rabies serology is important. Various laboratory methods can and have been used but serum neutralization methods have long been the gold standard due to the ability to measure function (neutralization), however these methods can be difficult to perform for several reasons. Assays such as enzyme linked absorbance assays (ELISA), indirect fluorescence antibody (IFA) and more recently lateral flow methods are in use. Interpretation of results can be problematic, not only between methods but also due to modifications of the same method that can lead to misinterpretations. A common assumption in review of laboratory test results is that different methods for the same component produce comparable results under all conditions or circumstances. Assumptions and misinterpretations provide the potential for detrimental decisions, ranging from regulatory to clinically related, and most importantly what ‘level’ is protective. Review of the common challenges in performance and interpretation of rabies serology and specific examples illuminate critical issues to consider when reviewing and applying results of rabies serological testing.

Anecdotal evidence suggests that the popular pastime of exploring one’s family history can unleash strong emotions, both positive and negative. The aim of this study was to chart the extent and nature of negative emotions among family historians, and profile those most vulnerable to distress. Data from an online survey of 775 adult Australian hobbyist family historians showed nearly two-thirds experienced strong distressing emotions such as anger, shock and sadness while researching their forebears. Triggers included discoveries which led to feelings of betrayal and distrust or posed moral dilemmas. Also distressing were findings about ancestors who behaved badly, were treated cruelly/unfairly, or who experienced tragedy. Family historians who reported strong negative emotions were more likely than those who did not to be younger, female, spend more time on their hobby, have half-siblings, driven by the motive for greater self-understanding, and score higher on the personality trait of openness to experience but lower on emotional stability. The study is important because it raises issues of (a) what support is available to family historians who find their discoveries strongly distressing and (b) whether purveyors of genealogical research products should provide more education and support to their clients.

The purpose of this paper is to discuss the idea that the misdeeds of ancestors will have negative consequences for their descendants, as encapsulated by biblical quotes about ‘the sins of the fathers’. The prevalence of these ideas in religion and folklore, through the notion of family curses, is discussed, as is an analysis of what constitutes ‘sin’. How the so-called sins of our forebears might reach across future generations is considered in two ways. The first is that detrimental characteristics, behaviours, and health conditions can be transmitted to descendants via genetic, epigenetic, environmental, and psychosocial mechanisms (and the interactions between these). The second is that descendants can feel guilt and shame as a result of the actions of their ancestors. Overcoming the effects of ancestral fault and disadvantage may occur through improvements in living standards, medical advances, more tolerant and inclusive cultural beliefs, as well as other environmental and social changes. These processes are also likely to be assisted by greater knowledge and understanding of one’s own family history. Such knowledge, in historical context, has the potential to facilitate both personal psychotherapeutic change and decisions about appropriate reparations where these are indicated.

Family historians frequently encounter ethical issues in the course of their research, and many come to recognise the moral dilemmas facing them. Common dilemmas revolve around topics such as whether family secrets should be revealed or favourite stories debunked in light of the evidence, how the privacy of living relatives can be maintained when family histories are published, if the ‘sins of the fathers’ require reparation (and how this might be possible), and to what extent is it acceptable to romanticise or ‘whitewash’ one’s ancestral story. In this paper, dilemmas such as these are discussed using the theoretical framework of psychologist Jonathan Haidt whose model of five moral ‘instincts’ includes care, fairness, loyalty, respect for authority, and sanctity. It is concluded that examining ethical issues using such a framework has the potential to stimulate empathy, reduce impulsive action, and increase the likelihood of finding creative solutions to moral dilemmas.

Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination.

Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization--the ability of antibody to inactivate virus infectivity, often measured in vitro--is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the \"gold standard\" assay to measure rabies virus-neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations-but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection.

Immunity from rabies depends on rabies virus neutralizing antibodies (RVNA) induced after immunization; however, the influence of antibody isotype switching has not been extensively investigated. This has become particularly relevant with changes in World Health Organization (WHO) recommended rabies vaccine regimens that may influence RVNA isotype kinetics, potentially affecting the peak, and longevity, of RVNA immunoglobulin (IgG) levels. We developed rapid and reliable assays for quantifying the anti-rabies IgM/IgG class switch in human serum based on an indirect ELISA technique. The immune response was tracked in ten individuals naïve to the rabies vaccine by quantifying serum titers weekly, from day seven to day 42 post-immunization, using a serum neutralization assay and the ELISA IgM/IgG assays. The average RVNA IU/mL levels were at D0 ≤ 0.1, D7 0.24, D14 8.36, D21 12.84, D28 25.74 and D42 28.68. Levels of specific IgM antibodies to rabies glycoprotein (EU/mL) were higher, on average, at D7, 1.37, and from D14, 5.49, to D21, 6.59. In contrast, average IgG antibodies (EU/mL) predominated from D28, 10.03, to D42, 14.45. We conclude that levels of anti-rabies IgM/IgG at D28 characterize the isotype class switch. These assays, combined with serum neutralization assays, distinguished the RVNA levels in terms of the IgM/IgG responses and are expected to add to the diagnostic repertoire, provide additional information in establishing rabies vaccine regimens, both post- and pre-exposure prophylaxis, and contribute to research efforts.

The idea for this Special Issue of Genealogy came from my fascination not just with my own family history research, but through my involvement with groups of other passionate fellow family history researchers [...]

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs' failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57-1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12-16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8-30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

The authors wish to make the following corrections to this paper [...]