Animal morbilliviruses and their cross-species transmission potential.

Like measles virus (MV), whose primary hosts are humans, non-human animal morbilliviruses use SLAM (signaling lymphocytic activation molecule) and PVRL4 (nectin-4) expressed on immune and epithelial cells, respectively, as receptors. PVRL4's amino acid sequence is highly conserved across species, while that of SLAM varies significantly. However, non-host animal SLAMs often function as receptors for different morbilliviruses. Uniquely, human SLAM is somewhat specific for MV, but canine distemper virus, which shows the widest host range among morbilliviruses, readily gains the ability to use human SLAM. The host range for morbilliviruses is also modulated by their ability to counteract the host's innate immunity, but the risk of cross-species transmission of non-human animal morbilliviruses to humans could occur if MV is successfully eradicated.

Evolutionary evidence for multi-host transmission of cetacean morbillivirus.

Cetacean morbillivirus (CeMV) has emerged as the pathogen that poses the greatest risk of triggering epizootics in cetacean populations worldwide, and has a high propensity for interspecies transmission, including sporadic infection of seals. In this study, we investigated the evolutionary history of CeMV by deep sequencing wild-type viruses from tissue samples representing cetacean species with different spatiotemporal origins. Bayesian phylogeographic analysis generated an estimated evolutionary rate of 2.34 × 10-4 nucleotide substitutions/site/year and showed that CeMV evolutionary dynamics are neither host-restricted nor location-restricted. Moreover, the dolphin morbillivirus strain of CeMV has undergone purifying selection without evidence of species-specific mutations. Cell-to-cell fusion and growth kinetics assays demonstrated that CeMV can use both dolphin and seal CD150 as a cellular receptor. Thus, it appears that CeMV can readily spread among multiple cetacean populations and may pose an additional spillover risk to seals.

Actualización situacion sarampion y acciones intensificadas de vigilancia y control / Update to measles situation and intensified actions on surveillance and control

El 28 de marzo de 2018 se confirmó un caso de sarampión en un bebe de 8 meses, residente de la Ciudad de Buenos Aires. En función de ello, y teniendo como escenario posible lo que está ocurriendo en la actualidad, desde el Ministerio de Salud de la CABA, se comenzaron a diseñar estrategias de abordaje de carácter preventivo, para promover el control de este evento en la población en general y, en particular, en los niños susceptibles: por un lado, todos los menores de 6 años que cuentan -o deberían contar- con al menos una dosis de triple viral (entre el año de vida y el inicio escolar) y, principalmente, aquellos que por calendario, no les corresponde vacunación (los menores de un año). El 19 de julio de 2018, a poco menos de 3 meses del caso confirmado previo (categorizado como "relacionado con la importación", luego de haber hallado la fuente de infección proveniente de Asia), se notificaron dos casos confirmados que se atendieron en efectores públicos de la Ciudad de Buenos Aires, un residente de CABA y otro de Provincia de Buenos Aires. En este apartado se actualiza la situación epidemiológica a la fecha y se detallan las acciones realizadas y por realizar para la prevención y control de este evento.(AU)

Model recommendations meet management reality: implementation and evaluation of a network-informed vaccination effort for endangered Hawaiian monk seals.

Where disease threatens endangered wildlife populations, substantial resources are required for management actions such as vaccination. While network models provide a promising tool for identifying key spreaders and prioritizing efforts to maximize efficiency, population-scale vaccination remains rare, providing few opportunities to evaluate performance of model-informed strategies under realistic scenarios. Because the endangered Hawaiian monk seal could be heavily impacted by disease threats such as morbillivirus, we implemented a prophylactic vaccination programme. We used contact networks to prioritize vaccinating animals with high contact rates. We used dynamic network models to simulate morbillivirus outbreaks under real and idealized vaccination scenarios. We then evaluated the efficacy of model recommendations in this real-world vaccination project. We found that deviating from the model recommendations decreased the efficiency; requiring 44% more vaccinations to achieve a given decrease in outbreak size. However, we gained protection more quickly by vaccinating available animals rather than waiting to encounter priority seals. This work demonstrates the value of network models, but also makes trade-offs clear. If vaccines were limited but time was ample, vaccinating only priority animals would maximize herd protection. However, where time is the limiting factor, vaccinating additional lower-priority animals could more quickly protect the population.

Transmission of morbilliviruses within and among marine mammal species.

Transmission of morbilliviruses within and among marine mammal species has been documented in a variety of marine habitats. Cetacean morbillivirus spreads between cetacean species in the aquatic environment whereas both phocine distemper virus and canine distemper virus have been associated with transmission within and between pinniped and terrestrial carnivore species in their natural habitat and at the aquatic-terrestrial interface. Periodically these viruses have caused large epizootics involving thousands of animals, due to sustained intra-species virus transmission. Social behavior of host species, marine habitat, geographical barriers and virus-host adaptations all likely contribute toward modulating virus spread. In combination with increased surveillance and whole genome sequencing, further research into ecological and host factors will be pivotal in better understanding the global transmission dynamics of marine morbilliviruses.

Measles vaccination: Threat from related veterinary viruses and need for continued vaccination post measles eradication.

Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The veterinary members are canine distemper virus (CDV), peste des petits ruminants virus (PPRV), Rinderpest Virus (RPV) as well as the marine morbilliviruses phocine distemper virus (PDV), dolphin morbillivirus (DMV) and porpoise morbillivirus (PMV). Morbilliviruses have a severe impact on humans and animal species. They confer diseases which have contributed to morbidity and mortality of the population on a global scale. There is substantial evidence from both natural and experimental infections that morbilliviruses can readily cross species barriers. Of most concern with regard to zoonosis is the more recently reported fatal infection of primates in Japan and China with strains of CDV which have adapted to this host. The close genetic relationship, shared cell entry receptors and similar pathogenesis between the morbilliviruses highlights the potential consequences of complete withdrawal of MV vaccination after eradication. Therefore, it would be prudent to continue the current MV vaccination. Ultimately development of novel, safe vaccines which have higher efficacy against the veterinary morbilliviruses is a priority. These would to protect the human population long term against the threat of zoonosis by these veterinary viruses.

Delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets.

Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (CDV) expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo). Six donor ferrets simultaneously received three rCDVs expressing green, red or blue fluorescent proteins via conjunctival (ocular, Oc), intra-nasal (IN) or intra-tracheal (IT) inoculation. Two days post-inoculation sentinel ferrets were placed in physically separated adjacent cages to assess airborne transmission. All donor ferrets developed lymphopenia, fever and lethargy, showed progressively increasing systemic viral loads and were euthanized 14 to 16 days post-inoculation. Systemic replication of virus inoculated via the Oc, IN and IT routes was detected in 2/6, 5/6 and 6/6 ferrets, respectively. In five donor ferrets the IT delivered virus dominated, although replication of two or three different viruses was detected in 5/6 animals. Single lymphocytes expressing multiple fluorescent proteins were abundant in peripheral blood and lymphoid tissues, demonstrating the occurrence of double and triple virus infections. Transmission occurred efficiently and all recipient ferrets showed evidence of infection between 18 and 22 days post-inoculation of the donor ferrets. In all cases, airborne transmission resulted in replication of a single-colored virus, which was the dominant virus in the donor ferret. This study demonstrates that morbilliviruses can use multiple entry routes in parallel, and co-infection of cells during viral dissemination in the host is common. Airborne transmission was efficient, although transmission of viruses expressing a single color suggested a bottleneck event. The identity of the transmitted virus was not determined by the site of inoculation but by the viral dominance during dissemination.

Diversity of susceptible hosts in canine distemper virus infection: a systematic review and data synthesis.

BACKGROUND: Canine distemper virus (CDV) is the etiological agent of one of the most infectious diseases of domestic dogs, also known as a highly prevalent viral infectious disease of carnivores and posing a conservation threat to endangered species around the world. To get a better panorama of CDV infection in different Orders, a retrospective and documental systematic review of the role of CDV in different non-dog hosts was conducted. The bibliographical data were collected from MedLine/PubMed and Scopus databases. Data related to Order, Family, Genus and Species of the infected animals, the presence or absence of clinical signs, mortality, serological, molecular or antigenic confirmation of CDV infection, geographic location, were collected and summarized. RESULTS: Two hundred seventeen scientific articles were considered eligible which includes reports of serological evaluation, and antigenic or genomic confirmation of CDV infection in non-dog hosts. CDV infects naturally and experimentally different members of the Orders Carnivora (in 12 Families), Rodentia (four Families), Primates (two Families), Artiodactyla (three Families) and Proboscidea (one Family). The Order Carnivora (excluding domestic dogs) accounts for the vast majority (87.5%) of the records. Clinical disease associated with CDV infection was reported in 51.8% of the records and serological evidence of CDV infection in apparently healthy animals was found in 49.5% of the records. High mortality rate was showed in some of the recorded infections in Orders different to Carnivora. In non-dog hosts, CDV has been reported all continents with the exception of Australasia and in 43 different countries. CONCLUSIONS: The results of this systematic review demonstrate that CDV is able to infect a very wide range of host species from many different Orders and emphasizes the potential threat of infection for endangered wild species as well as raising concerns about potential zoonotic threats following the cessation of large-scale measles vaccination campaigns in the human population.

Mapping the evolutionary trajectories of morbilliviruses: what, where and whither.

Morbilliviruses are pathogens of humans and other animals. Live attenuated morbillivirus vaccines have been used to end endemic transmission of measles virus (MV) in many parts of the developed world and to eradicate rinderpest virus. Entry is mediated by two different receptors which govern virus lymphotropism and epitheliotropism. Morbillivirus transmissibility is unparalleled and MV represents the most infectious human pathogen on earth. Their evolutionary origins remain obscure and their potential for adaption to new hosts is poorly understood. It has been suggested that MV could be eradicated. Therefore it is imperative to dissect barriers which restrict cross species infections. This is important as ecological studies identify novel morbilliviruses in a vast number of small mammals and carnivorous predators.

Morbillivirus infections: an introduction.

Research on morbillivirus infections has led to exciting developments in recent years. Global measles vaccination coverage has increased, resulting in a significant reduction in measles mortality. In 2011 rinderpest virus was declared globally eradicated - only the second virus to be eradicated by targeted vaccination. Identification of new cellular receptors and implementation of recombinant viruses expressing fluorescent proteins in a range of model systems have provided fundamental new insights into the pathogenesis of morbilliviruses, and their interactions with the host immune system. Nevertheless, both new and well-studied morbilliviruses are associated with significant disease in wildlife and domestic animals. This illustrates the need for robust surveillance and a strategic focus on barriers that restrict cross-species transmission. Recent and ongoing measles outbreaks also demonstrate that maintenance of high vaccination coverage for these highly infectious agents is critical. This introduction briefly summarizes the most important current research topics in this field.

Cetacean morbillivirus: current knowledge and future directions.

We review the molecular and epidemiological characteristics of cetacean morbillivirus (CeMV) and the diagnosis and pathogenesis of associated disease, with six different strains detected in cetaceans worldwide. CeMV has caused epidemics with high mortality in odontocetes in Europe, the USA and Australia. It represents a distinct species within the Morbillivirus genus. Although most CeMV strains are phylogenetically closely related, recent data indicate that morbilliviruses recovered from Indo-Pacific bottlenose dolphins (Tursiops aduncus), from Western Australia, and a Guiana dolphin (Sotalia guianensis), from Brazil, are divergent. The signaling lymphocyte activation molecule (SLAM) cell receptor for CeMV has been characterized in cetaceans. It shares higher amino acid identity with the ruminant SLAM than with the receptors of carnivores or humans, reflecting the evolutionary history of these mammalian taxa. In Delphinidae, three amino acid substitutions may result in a higher affinity for the virus. Infection is diagnosed by histology, immunohistochemistry, virus isolation, RT-PCR, and serology. Classical CeMV-associated lesions include bronchointerstitial pneumonia, encephalitis, syncytia, and lymphoid depletion associated with immunosuppression. Cetaceans that survive the acute disease may develop fatal secondary infections and chronic encephalitis. Endemically infected, gregarious odontocetes probably serve as reservoirs and vectors. Transmission likely occurs through the inhalation of aerosolized virus but mother to fetus transmission was also reported.

Receptor interactions, tropism, and mechanisms involved in morbillivirus-induced immunomodulation.

Induction of immunomodulation and -suppression is a common feature of morbilliviruses such as measles virus (MV), rinderpest virus (RPV), and canine distemper virus (CDV) in their respective hosts. As major uptake receptor, signaling lymphocytic activation molecule (SLAM, CD150) essentially determines their tropism for immune cells, which is of considerable importance with regard to immunosuppression and the systemic spread to organs including secondary lymphoid organs, the skin, the respiratory tract, and the brain. Independent of their ability to enhance virus uptake in specialized host cells, other cell surface receptors such as the substance P receptor, DC-SIGN, Toll-like receptors (TLR), Fc-gamma receptor II (FcgammaRII), CD46, and additional uncharacterized receptors exert a variety of immunomodulatory effects as reflected by activation of or interference with viability, differentiation, trafficking, or acquisition of effector functions of specialized immune cells. In this review, we discuss receptor interactions, tropism, and mechanisms involved in the severe, transient immunosuppression induced by MV and other morbilliviruses.

The duration of a sequence of epidemics.

The typical duration of an epidemic in a sequence of linearly ordered populations shows a surprising nonmonotonic behaviour with respect to population size, which was noted by Swinton (1998) [Bull. Math. Biol., 60, 215-230]. This paper gives the sketch of a proof of the phenomenon.

Catastrophes after crossing species barriers.

Probably the most tragic examples of virus infections that have caused the deaths of many millions of people in the past century were the influenza and AIDS pandemics. These events occurred as a direct result of the introduction of animal viruses into the human population. Similarly, mass mortalities among aquatic and terrestrial mammals were caused by the introduction of viruses into species in which they had not previously been present. It seems paradoxical that at a time when we have managed to control or even eradicate major human virus infections like polio and smallpox we are increasingly confronted with new or newly emerging virus infections of humans and animals. A complex mix of social, technological and ecological changes, and the ability of certain viruses to adapt rapidly to a changing environment, seems to be at the basis of this phenomenon. Extensive diagnostic and surveillance networks, as well as novel vaccine- and antiviral development strategies should provide us with the safeguards to limit its impact.

Identification of morbilliviruses of probable cetacean origin in carcases of Mediterranean monk seals (Monachus monachus).

Two morbilliviruses were isolated from carcases of Mediterranean monk seals (Monachus monachus) which had died in coastal areas of Greece and Mauritania. They were characterised as being closely related to the previously identified dolphin and porpoise morbilliviruses on the basis of their serological cross-reactivities in immunofluorescence assays, and sequence homologies in their N and P genes. The results suggest that morbilliviruses of aquatic mammals may cross barriers between species of different orders.

Transmissibility from horses to humans of a novel paramyxovirus, equine morbillivirus (EMV).

OBJECTIVES: Determination of potential infectivity of a new paramyxovirus equine morbillivirus (EMV) from horses to humans and humans to humans as a result of two outbreaks in Queensland which involved 23 horses and three humans. METHODS: Seroepidemiological testing using neutralizing and immunofluorescing antibodies on people with variable levels of exposure to infected horses and humans. RESULTS: All serological testing on a total of 298 individual contacts was negative. CONCLUSIONS: While the three human cases of EMV were probably infected as a result of very close contact with horses, these data suggest that infectivity from horses or humans is very low.

Modelling the spread of phocine distemper virus among harbour seals.

Data presented in earlier publications on the 1988 epizootic among seals in North West Europe show a pattern that is somewhat inconsistent with the predictions of the standard mathematical model of epidemics. We argue that for animals living in herds or colonies, such as seals, the mutual contact behaviour is such that models for the transmission of infectious diseases should be applied with special care for the distinction between numbers and densities. This is demonstrated by using a mechanistic description of the contacts among seals, which leads to a slightly different formulation of the model. Results of the analysis of this formulation are more in line with the data. The model introduced here can be applied to epidemics among all kinds of animals living in herds and in fact to any species with constant local density, independent of the total population size (i.e., occupying a variable area). Application of the traditional formulation, using different parameters for herds of different sizes, will give equally good results for non-lethal diseases. However, especially for diseases with a low R0 and high death rates, such as the phocine distemper virus (PDV) disease, the two model formulations give quite different results. Further analysis of the model is performed to determine the most important factors influencing such an epidemic. The survival of infected animals turns out to have a disproportionately great influence on the intensity of the epidemic. Therefore in the case of the PDV epizootic we conclude that marine pollution may not only have contributed to the high death rates, but, if so, it has intensified the epizootic as well.