Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case ...definitions, standardized diagnostic approaches, and priorities for research. Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.
Abstract Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ...ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies. The studies included healthy adult subjects in the USA and India and involved two parts. First, subjects received a single intramuscular dose of CL184 or placebo in a double blind, randomized, dose-escalation trial. Second, open-label CL184 (20 IU/kg) was co-administered with rabies vaccine. Safety was the primary objective and rabies virus neutralizing activity (RVNA) was investigated as efficacy parameter. Pain at the CL184 injection site was reported by less than 40% of subjects; no fever or local induration, redness or swelling was observed. RVNA was detectable from day 1 to day 21 after a single dose of CL184 20 or 40 IU/kg. All subjects had adequate (>0.5 IU/mL) RVNA levels from day 14 onwards when combined with rabies vaccine. CL184 appears promising as an alternative to RIG in PEP.
The ecology of infectious disease in wildlife has become a pivotal theme in animal and public health. Studies of infectious disease ecology rely on robust surveillance of pathogens in reservoir ...hosts, often based on serology, which is the detection of specific antibodies in the blood and is used to infer infection history. However, serological data can be inaccurate for inference to infection history for a variety of reasons. Two major aspects in any serological test can substantially impact results and interpretation of antibody prevalence data: cross-reactivity and cut-off thresholds used to discriminate positive and negative reactions. Given the ubiquitous use of serology as a tool for surveillance and epidemiological modeling of wildlife diseases, it is imperative to consider the strengths and limitations of serological test methodologies and interpretation of results, particularly when using data that may affect management and policy for the prevention and control of infectious diseases in wildlife. Greater consideration of population age structure and cohort representation, serological test suitability and standardized sample collection protocols can ensure that reliable data are obtained for downstream modeling applications to characterize, and evaluate interventions for, wildlife disease systems.
Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization ...for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.
Background. This article describes multiple transmissions of rabies via transplanted solid organ from a single infected donor. The empirical Milwaukee treatment regimen was used in the recipients. ...Methods. Symptomatic patients were treated by deep sedation (ketamine, midazolam, and phenobarbital), ribavirin, interferon, and active and passive vaccination. Viral loads and antibodies were continuously monitored. Results. Recipients of both cornea and liver transplants developed no symptoms. The recipient of the liver transplant had been vaccinated ∼20 years before transplantation. Two recipients of kidney and lung transplants developed rabies and died within days of symptomatic disease. Another kidney recipient was treated 7 weeks before he died. The cerebrospinal fluid viral load remained at constant low levels (<10,000 copies/mL) for ∼5 weeks; it increased suddenly by almost 5 orders of magnitude thereafter. After death, no virus was found in peripheral compartments (nerve tissue, heart, liver, or the small intestine) in this patient, in contrast to in patients in the same cohort who died early. Conclusions. Our report includes, to our knowledge, the longest documented treatment course of symptomatic rabies and the first time that the virus concentration was measured over time and in different body compartments. The postmortem virus concentration in the periphery was low, but there was no evidence of a reduction of virus in the brain.
Abstract Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental ...chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials.
Bats are natural reservoirs for the majority of lyssaviruses globally, and are unique among mammals in having exceptional sociality and longevity. Given these facets, and the recognized status of ...bats as reservoirs for rabies viruses (RABVs) in the Americas, individual bats may experience repeated exposure to RABV during their lifetime. Nevertheless, little information exists with regard to within-host infection dynamics and the role of immunological memory that may result from abortive RABV infection in bats. In this study, a cohort of big brown bats (Eptesicus fuscus) was infected intramuscularly in the left and right masseter muscles with varying doses 10(-0.1)-10(4.9) median mouse intracerebral lethal doses (MICLD(50)) of an E. fuscus RABV variant isolated from a naturally infected big brown bat. Surviving bats were infected a second time at 175 days post-(primary) infection with a dose (10(3.9)-10(4.9) MICLD(50)) of the same RABV variant. Surviving bats were infected a third time at either 175 or 305 days post-(secondary) infection with a dose (10(4.9) MICLD(50)) of the same RABV variant. When correcting for dose, similar mortality was observed following primary and secondary infection, but reduced mortality was observed following the third and last RABV challenge, despite infection with a high viral dose. Inducible RABV-neutralizing antibody titres post-infection were ephemeral among infected individuals, and dropped below levels of detection in several bats between subsequent infections. These results suggest that long-term repeated infection of bats may confer significant immunological memory and reduced susceptibility to RABV infection.
Rhabdoviruses (family
Rhabdoviridae) include a diversity of important pathogens of animals and plants. They share morphology and genome organization. The understanding of rhabdovirus phylogeny, ...ecology and evolution has progressed greatly during the last 30 years, due to enhanced surveillance and improved methodologies of molecular characterization. Along with six established genera, several phylogenetic groups at different levels were described within the
Rhabdoviridae. However, comparative relationships between viral phylogeny and taxonomy remains incomplete, with multiple representatives awaiting further genetic characterization. The same is true for rhabdovirus evolution. To date, rather simplistic molecular clock models only partially describe the evolutionary dynamics of postulated viral lineages. Ongoing progress in viral evolutionary and ecological investigations will provide the platform for future studies of this diverse family.
The direct and interactive effects of climate change on host species and infectious disease dynamics are likely to initially manifest\ at latitudinal extremes. As such, Alaska represents a region in ...the United States for introspection on climate change and disease. Rabies is enzootic among arctic foxes (Vulpes lagopus) throughout the northern polar region. In Alaska, arctic and red foxes (Vulpes vulpes) are reservoirs for rabies, with most domestic animal and wildlife cases reported from northern and western coastal Alaska. Based on passive surveillance, a pronounced seasonal trend in rabid foxes occurs in Alaska, with a peak in winter and spring. This study describes climatic factors that may be associated with reported cyclic rabies occurrence. Based upon probabilistic modelling, a stronger seasonal effect in reported fox rabies cases appears at higher latitudes in Alaska, and rabies in arctic foxes appear disproportionately affected by climatic factors in comparison with red foxes. As temperatures continue a warming trend, a decrease in reported rabid arctic foxes may be expected. The overall epidemiology of rabies in Alaska is likely to shift to increased viral transmission among red foxes as the primary reservoir in the region. Information on fox and lemming demographics, in addition to enhanced rabies surveillance among foxes at finer geographic scales, will be critical to develop more comprehensive models for rabies virus transmission in the region.
Highlights • Investigated prevalence of antibodies against canine adenovirus (CAV) in South African dogs. • High level of antibodies against CAV present in dog populations (40–60%). • Evaluated ...recombinant CAV2 vaccine expressing rabies virus glycoprotein in presence of CAV antibodies. • Presence of CAV antibodies hampers RABV-specific seroconversion in dogs.
PDF
