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.

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.

MODELING A MORBILLIVIRUS OUTBREAK IN HAWAIIAN MONK SEALS (NEOMONACHUS SCHAUINSLANDI) TO AID IN THE DESIGN OF MITIGATION PROGRAMS.

We developed a stochastic susceptible-exposed-infectious-removed (SEIR) model to simulate a range of plausible morbillivirus outbreak scenarios in a randomly mixing population of 170 endangered Hawaiian monk seals (Neomonachus schauinslandi). We then modeled realistic vaccination and quarantine measures to determine the potential efficacy of such mitigation efforts. Morbillivirus outbreaks represent substantial risk to monk seals-91% of simulated baseline outbreaks grew (R0>1), and in one-third of the scenarios all, or nearly all, individuals were infected. Simulated vaccination efforts in response to an outbreak were not effective in substantially reducing infections, largely because of the prolonged interval between vaccination and immunity. Prophylactic vaccination, in contrast, could be an effective tool for preventing outbreaks. Herd immunity is practically achievable because of the small sizes of monk seal populations and the animals' accessibility on shore. Adding realistic spatial structure to the model, as informed by movement of seals tracked in the main Hawaiian Islands with the use of telemetry, greatly reduced the simulated impact of outbreaks (≤10 seals were infected in 62% of spatially structured simulations). Although response vaccination remained relatively ineffective, spatial segregation allowed herd immunity to be achieved through prophylactic vaccination with less effort. In a randomly mixing population of 170 seals, 86% would need to be vaccinated to achieve herd immunity in 95% of simulated outbreaks, compared to only approximately 60% in three spatially segregated subgroups with the same combined abundance. Simulations indicate that quarantining a modest number (up to 20) of ill seals has the potential to extinguish even fast-growing outbreaks rapidly. The efficacy of quarantine, however, is highly dependent upon rapid detection and response. We conclude that prophylactic vaccination combined with a quarantine program supported by vigilant surveillance and rapid, reliable diagnosis could greatly mitigate the threat of a morbillivirus outbreak in Hawaiian monk seals.

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.

[Pregnancy and vaccinoprevention].

Vaccinations protect woman and her fetus against different infectious diseases, but their application on pregnant should be extremely responsible. In this review I present information about some infectious diseases and vaccines during pregnancy. Women, planning to get pregnant should be advised to do serological tests in order to find out their immune status against some infections, leading to fetal congenital malformations (rubella, chicken pox, hepatitis B) and if necessary to get vaccinated at least a month before pregnancy. Despite the lack of vaccines against Cytomegalovirus (CMV), parvovirus 19 and Toxoplasma gondii it is good to know woman's immune status against these infections in order to clarify the clinical approach in case of future contact with sick or carriers. Parvovirus 19 could cause fetal death, while CMV could be transmitted to the child. Immune women wouldn't get sick and wouldn't transmit Toxoplasmagondii to the fetus during pregnancy. Recommended vaccines before pregnancy include vaccines against flu, human papilloma virus, MMR (morbilli, measles, rubella), Tdap (tetanus, diphtheria, whooping cough), chicken pox. CDC-Atlanta recommends during pregnancy two vaccines--against flu, in case it wasn't done before pregnancy, and Tdap during every pregnancy between 27-th and 36-th gestation week. Whooping cough is very dangerous for the baby during the first two months after birth, while it is not yet vaccinated. From this point of view it is of best interest of the mother to have strong immunity in order to transfer antibodies during breastfeeding, as well as for the father and the rest who will take care for the newborn child to be vaccinated against whooping cough. During pregnancy vaccinations against tuberculosis, morbilli, measles, rubella, meningococcal disease, typhoid fever and chicken pox are contraindicated. In case of contact vaccinations against rabies, anthrax, small pox, poliomyelitis and yellow fever should be taken into consideration. Immediately after birth, if the vaccination against whooping cough is missed young mother vaccination is recommended. The vaccination is one of the greatest achievements of the modern medicine, but it is still an object of vigorous attacks, concerning used products safety. One of the most spreading fears is about sterility after vaccination. Over a period of three years (2009-2012) 563 women were vaccinated by SACMEH against HPV. Forty two of them (13.40%) interrupt vaccination due to pregnancy (18 of them after the first shot and 24 after the second shot). Our observations show, that this vaccine is carried out good by the patients, tit is safe and does not cause sterility.

Morbillivirus vaccines: recent successes and future hopes.

The impact of morbilliviruses on both human and animal populations is well documented in the history of mankind. Indeed, prior to the development of vaccines for these diseases, morbilliviruses plagued both humans and their livestock that were heavily relied upon for food and motor power within communities. Measles virus (MeV) was responsible for the death of millions of people annually across the world and those fortunate enough to escape the disease often faced starvation where their livestock had died following infection with rinderpest virus (RPV) or peste des petits ruminants virus (PPRV). Canine distemper virus has affected dog populations for centuries and in the past few decades appears to have jumped species, now causing disease in a number of non-canid species, some of which are been pushed to the brink of extinction by the virus. During the age of vaccination, the introduction and successful application of vaccines against rinderpest and measles has led to the eradication of the former and the greater control of the latter. Vaccines against PPR and canine distemper have also been generated; however, the diseases still pose a threat to susceptible species. Here we review the currently available vaccines against these four morbilliviruses and discuss the prospects for the development of new generation vaccines.

Serologic response of harbor seals (Phoca vitulina) to vaccination with a recombinant canine distemper vaccine.

Morbilliviruses pose a significant threat to marine mammal populations around the world and have been associated with multiple epizootics in pinnipeds and cetaceans. As part of a preventive veterinary medical program, five harbor seals (Phoca vitulina) in a managed collection were vaccinated with a recombinant canarypox-vectored canine distemper virus vaccine. The vaccine was evaluated for safety (by monitoring seals for local and systemic adverse effects and by testing for shedding of the canarypox vector) and efficacy (by testing for serum neutralizing antibodies). None of the seals showed signs of local or systemic adverse reactions to the vaccination. Three seals vaccinated once did not seroconvert, but the recombinant vaccine induced a persistent serum virus neutralizing titer (12 mo) in the two seals that were vaccinated twice, 1 mo apart.

A DNA vaccine against dolphin morbillivirus is immunogenic in bottlenose dolphins.

The immunization of exotic species presents considerable challenges. Nevertheless, for facilities like zoos, animal parks, government facilities and non-profit conservation groups, the protection of valuable and endangered species from infectious disease is a growing concern. The rationale for immunization in these species parallels that for human and companion animals; to decrease the incidence of disease. The U.S. Navy Marine Mammal Program, in collaboration with industry and academic partners, has developed and evaluated a DNA vaccine targeting a marine viral pathogen - dolphin morbillivirus (DMV). The DMV vaccine consists of the fusion (F) and hemagglutinin (H) genes of DMV. Vaccine constructs (pVR-DMV-F and pVR-DMV-H) were evaluated for expression in vitro and then for immunogenicity in mice. Injection protocols were designed for application in Atlantic bottlenose dolphins (Tursiops truncatus) to balance vaccine effectiveness with clinical utility. Six dolphins were inoculated, four animals received both pDMV-F and pDMV-H and two animals received a mock vaccine (vector alone). All animals received an inoculation week 0, followed by two booster injections weeks 8 and 14. Vaccine-specific immune responses were documented in all four vaccinated animals. To our knowledge, this is the first report of pathogen-specific immunogenicity to a DNA vaccine in an aquatic mammal species.

Development of new generation rinderpest vaccines.

Veterinary science has benefited much from the advances in biotechnology during the past 20 years. New and improved diagnostic techniques for infectious diseases have been developed and new and highly effective vaccines to prevent such diseases have been introduced and more have been, or are about to be, field-tested. The latest development in negative strand virology, reverse genetics, the ability to rescue live virus from a DNA copy of the RNA genome, is being used to address questions concerning virus pathogenicity at the molecular level and to produce "marker" vaccines, i.e. vaccines that allow serological identification of all vaccinated animals. Such a vaccine would greatly benefit the continuing campaign for the global eradication of rinderpest since it would then be possible, by serological means, to detect wild type virus circulating in local areas or regions where it is still necessary to vaccinate and where the vaccination levels are below those required to eliminate the virus. Here we describe different approaches we have taken to produce such a vaccine using reverse genetics to add a marker to the existing and widely used Plowright rinderpest vaccine.

Xerovac: an ultra rapid method for the dehydration and preservation of live attenuated Rinderpest and Peste des Petits ruminants vaccines.

The accepted procedure for the long-term preservation of live viruses and bacteria in vaccines has been lyophilisation. We show that thermolabile viruses can be dehydrated in vitro, within 18 h, in an excipient containing trehalose. We further demonstrate that in the resulting dehydrated state, where the viruses are captive in a metastable glass composed of trehalose, they are capable of resisting 45 degrees C for a period of 14 days with minimal loss of potency. The degree of thermotolerance achieved matches that of current 'thermostable' lyophilised vaccines, but with the distinct advantage of a shorter, cheaper and simpler process. The development and utilisation of this process can make significant improvements in current live virus vaccine production. It presents a further step away from dependence on mandatory low temperature refrigerated storage and could lead to greater confidence in vaccine stability, potency and efficacy.

Economics of prophylaxis against peste des petits ruminants and gastrointestinal helminthosis in small ruminants in north Cameroon.

Data on reproduction and mortality were collected over one year from 5100 sheep and 13,300 goats in treated and control flocks. The treated animals received vaccination against peste des petits ruminants (PPR) and anthelmintics twice a year. Productivity parameters (fecundity and mortality rates) obtained with and without prophylaxis were fitted into a benefit-cost economic analysis model and run for project lifespans varying from one to five years. At a 7% discount rate, the overall benefits for a project lifespan of five years were estimated as over 15 million FCFA and 11 million FCFA for sheep and goats, respectively. The benefit-cost ratio ranged from 2.26 to 3.27 in goats and 3.01 to 4.23 in sheep, depending on the project lifespan. It was concluded that PPR and gastrointestinal helminthosis are important causes of economic losses in small ruminants in Cameroon. A national or even a regional vaccination campaign against PPR and strategic anthelmintic treatment of small ruminants are recommended.

Protective vaccination of ferrets against canine distemper with recombinant pox virus vaccines expressing the H or F genes of rinderpest virus.

OBJECTIVE: To investigate the ability of rinderpest virus (RPV) antigens, expressed in pox virus vectors, to protect against canine distemper virus (CDV) infection in ferrets. ANIMALS: Ferrets (Mustela putorius; n = 27) with no previous exposure to CDV. PROCEDURE: Ferrets were inoculated intradermally with recombinant vaccinia viruses expressing the H gene of RPV, the F gene of RPV, the H and F genes of RPV, or fowlpox virus recombinant expressing both genes. Two ferrets were vaccinated s.c. with CDV vaccine as positive controls, and 1 group was left unvaccinated as a negative control. Blood was obtained from ferrets biweekly; antibody titer to RPV was detected by ELISA, and CDV antibody titer was measured by serum neutralization testing and ELISA. RESULTS: Partial protection was seen in all groups, with vRVFH vaccination being the most protective (60%). CONCLUSIONS AND CLINICAL RELEVANCE: A single inoculation with a vaccinia virus expressing the H and F genes of RPV was able to protect 60% of the vaccinated ferrets challenge exposed with a high dose of CDV. These results indicate the ability of RPV antigens expressed by vaccinia virus to protect ferrets against a related morbillivirus. Further, they document the safety and efficacy of a recombinant vaccinia virus vaccine for ferrets. Such vaccines may be useful given the susceptibility of ferrets to CDV and the problem of maternal antibody interfering with vaccination of young animals.

Rinderpest and other animal morbillivirus infections: comparative aspects and recent developments.

The genus morbillivirus presently comprises measles virus of man, rinderpest virus (RPV), peste des petits ruminants virus (PPRV), and canine distemper virus (CDV). 'Emerging' morbilliviruses, such as phocid distemper virus (PDV) of seals, dolphin (DMV) and porpoise morbillivirus (PMV) have probably been present for a long period of time and outbreaks are possibly related to introduction into a highly susceptible population and/or be the result of interspecies transmission. In this review some comparative aspects of morbillivirus infections, particularly with respect to rinderpest and canine distemper viruses, are presented. Topics include pathogenesis, epidemiology, molecular phylogeny, diagnosis and prophylaxis. Recent developments in molecular biology have created tools which have enabled us to achieve a better understanding of morbillivirus infections at the nucleic acid level ('molecular epidemiology') while recombinant DNA technology has allowed new bivalent recombinant vaccines with improved heat stability to be produced.

Protection of goats against peste des petits ruminants with recombinant capripoxviruses expressing the fusion and haemagglutinin protein genes of rinderpest virus.

Goats were protected against a lethal challenge of peste des petits ruminants (PPR) virus following vaccination with a recombinant capripoxvirus containing either the fusion (F) gene of rinderpest virus or the haemagglutinin (H) gene of rinderpest virus. The H gene recombinant produced high titres of neutralizing antibody to rinderpest virus in the vaccinated goats, whereas the F gene recombinant failed to stimulate detectable levels of neutralizing antibody. A similar response to the two recombinant vaccines has previously been reported for cattle. Neither recombinant produced detectable levels of specific antibodies to PPR virus.