Benefit-cost analysis of coordinated strategies for control of rabies in Africa.

Previous research suggests that dog mass vaccination campaigns can eliminate rabies locally, resulting in large human and animal life gains. Despite these demonstrated benefits, dog vaccination programs remain scarce on the African continent. We conducted a benefit-cost analysis to demonstrate that engaging into vaccination campaigns is the dominant strategy for most countries even in the absence of coordinated action between them. And quantify how coordinated policy measures across countries in Africa could impact rabies incidence and associated costs. We show that coordinated dog mass vaccination between countries and PEP would lead to the elimination of dog rabies in Africa with total welfare gains of USD 9.5 billion (95% CI: 8.1 - 11.4 billion) between 2024 and 2054 (30 years). Coordinated disease control between African countries can lead to more socially and ecologically equitable outcomes by reducing the number of lost human lives to almost zero and possibly eliminating rabies.

Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex.

The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes. Our analysis identifies 89 novel miRNA transcripts, 48 of which undergo Dicer-dependent biogenesis and are loaded onto the Argonaute silencing complex. Several of the identified mature miRNA and pre-miRNA transcripts are unique to specific MHC haplotypes and overlap common SNPs. Furthermore, 43 of the 89 identified novel miRNA transcripts lie within linkage disequilibrium blocks that contain a disease-associated SNP. These disease associated SNPs are associated with 65 unique disease phenotypes, suggesting that these transcripts may play a role in the etiology of numerous diseases associated with the MHC. Additional in silico analysis reveals the potential for thousands of putative pre-miRNA encoding loci within the MHC that may be expressed by different cell types and at different developmental stages.

Rabies in dogs, livestock and wildlife: a veterinary perspective.

While major progress has been made in the control of rabies in the Western Hemisphere, large parts of Europe and some parts of Asia, the disease continues to kill tens of thousands of people every year. Its highest burden is in resourcelimited countries in Asia and Africa, disproportionately affecting children and poor rural communities. Today, domesticated dogs are responsible for the vast majority of human rabies cases. In late 2015, rabies experts from around the world gathered at the Rabies Global Conference in Geneva, Switzerland, and launched the ambitious initiative to end deaths from dog-mediated human rabies by 2030. The most cost-effective and sustainable approach to achieve this goal is to eliminate the disease at source through mass dog vaccination. In this article, the role of and challenges faced by Veterinary Services in resourcelimited settings in implementing the dog vaccination strategy to reduce the human rabies burden are discussed, together with the role of wildlife in disease control and why the 'One Health' approach is indispensable on the path towards a dograbies- free future.

Malgré les progrès considérables accomplis en matière de lutte contre la rage dans l'hémisphère occidental, dans une grande partie de l'Europe et en certains endroits d'Asie, la maladie continue à faire plusieurs dizaines de milliers de victimes chaque année dans le monde. Ce sont les pays à faibles ressources d'Asie et d'Afrique qui sont les plus touchés, avec une majorité écrasante de victimes parmi les enfants et dans les communautés rurales pauvres. Aujourd'hui, les chiens domestiques sont de loin la principale cause des cas de rage humaine. En décembre 2015, des experts du monde entier réunis à Genève (Suisse) à l'occasion de la Conférence mondiale sur la rage intitulée « Élimination mondiale de la rage humaine transmise par les chiens : agissons maintenant ! ¼ ont lancé une initiative ambitieuse visant à mettre fin aux décès humains dus à la rage transmise par les chiens d'ici 2030. La méthode la plus efficace et durable pour atteindre cet objectif consiste à éliminer la maladie à sa source au moyen de la vaccination massive des chiens. Les auteurs examinent le rôle des Services vétérinaires et les difficultés auxquelles ceux-ci sont confrontés lorsqu'ils entreprennent d'appliquer une stratégie de vaccination des chiens destinée à réduire le fardeau de la rage humaine dans un contexte de ressources limitées. Ils évoquent également l'importance de prendre en compte la faune sauvage dans le cadre du contrôle de la rage et expliquent en quoi l'approche « Une seule santé ¼ est incontournable pour avancer vers l'objectif d'un monde indemne de rage canine.

Aunque la lucha antirrábica ha conocido avances muy sustanciales en el hemisferio occidental, grandes partes de Europa y ciertas zonas de Asia, la enfermedad sigue matando a decenas de miles de personas al año. La carga más elevada de rabia se da en países con escasos recursos de Asia y África, donde la enfermedad afecta desproporcionadamente a los niños y a las comunidades rurales pobres. A día de hoy, los perros domésticos son responsables de la inmensa mayoría de los casos de rabia humana. A finales de 2015, especialistas del mundo entero se dieron cita en Ginebra (Suiza) para celebrar la conferencia mundial titulada «Eliminación mundial de la rabia humana transmitida por perros. ¡Actuemos ahora!¼ y poner en marcha la ambiciosa iniciativa de acabar con las muertes por rabia transmitida por perros como muy tarde en 2030. Para cumplir este objetivo, el método más sostenible y más eficaz en relación con el costo consiste en eliminar la enfermedad en su foco de origen, procediendo para ello a vacunaciones masivas de perros. Los autores exponen la función de los Servicios Veterinarios y las dificultades que afrontan en situaciones de escasez de recursos a la hora de aplicar la estrategia de vacunación canina para reducir la carga de rabia humana, así como el papel de la fauna silvestre en el control de la enfermedad y la razón por la cual es indispensable aplicar los planteamientos de «Una sola salud¼ para avanzar hacia un futuro libre de rabia.

Persistence of brucellosis in pastoral systems.

Regarded as a highly contagious, zoonotic disease with worldwide distribution, brucellosis is endemic in many countries and settings and is responsible for a considerable economic and health-related burden. Limited information is available on the persistence and prevalence of brucellosis in pastoral communities, due to the difficulty in gathering information and to their mobility. However, since these communities are economically and culturally dependent on livestock, it is important to further determine the cause of persistent disease and develop possible methods for its management. The two main objectives of this paper are to review the literature, identifying various epidemiological and social factors that affect the persistence of brucellosis in pastoral ecosystems, and determine prevalence estimates within these communities. The general trend of the summarised studies indicates low-level, relatively stable transmission of brucellosis in pastoral areas, when compared to transmission in intensive and semi-intensive peri-urban production systems. A formal mathematical analysis can be undertaken using matrix models or coupled differential equations. This allows an examination of the various conditions under which the number of diseased, infected or exposed animals remains stable. The authors examined an existing mathematical differential equation model for brucellosis in Mongolia for its equilibrium conditions and found it reasonably robust, though clearly more data are needed to estimate threshold densities for brucellosis transmission in other regions of the world. However, the results indicate the importance of livestock demographic determinants for brucellosis persistence. The paper concludes that brucellosis remains largely persistent in pastoral areas of the world, despite (varying) control efforts. Plans to control brucellosis in pastoral settings should include ecological considerations, such as sustaining ecosystem services in pastoral areas. This approach would include placing limitations on livestock stocking density, land reform, improved governance and integrated social and economic development.

Towards a comprehensive simulation model of malaria epidemiology and control.

Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium- and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programmes.

Induction of apoptosis by iridovirus virion protein extract.

Chilo iridescent virus (CIV; IIV-6) is the type member of the genus Iridovirus (family Iridoviridae, large icosahedral cytoplasmic DNA viruses). CIV induces death and deformity in the cotton boll weevil, Anthonomus grandis, replicates productively in larvae of the cotton boll weevil, and significantly reduces laboratory populations of the cotton aphid, Aphis gossypii. CIV virion protein extract (CVPE) shuts down host protein synthesis in several insect cell lines and induces mortality in neonate boll weevil larvae. We report here that CVPE induces apoptosis in spruce budworm and boll weevil cell lines, as detected by blebbing, DNA fragmentation, and TUNEL assay. Tissue culture toxicity dose assays (TCTD(50)) showed that spruce budworm cells were eight times more sensitive to CVPE than boll weevil cells. Pancaspase inhibitor suppressed apoptosis but had marginal effect on inhibition of host protein synthesis. Moreover, the CVPE dose for apoptosis was 1000-fold lower than the dose for shutdown of host synthesis. We also detected protein kinase activity in CVPE. Heating CVPE at 60 degrees C for 30 min destroyed all three activities. Our results suggest that one or more polypeptides in CIV induce apoptosis. This is the first study demonstrating apoptosis induction by a member of the genus Iridovirus and by virion extracts of a member of the family Iridoviridae.

Immune response to syngeneic spermatozoa & its effect on target organs in mice.

Two groups of adult Swiss mice were immunised with washed syngeneic spermatozoa without any adjuvant for a period of two months or four months respectively. The presence of antibodies to spermatozoa was measured by micro sperm-agglutination and micro sperm-immobilization tests. The development of cell mediated immune response (CMIR) was measured by leucocyte migration inhibition test (LMIT) using spermatozoal antigens solubilized by 3M KCl, Nonidet P-40 or by subjecting the cells to ultrasonication. SDS-PAGE analysis of these proteins indicated that extraction of spermatozoa with 3 M KCl was a better method for solubilization of antigens present on sperm membrane. Almost all immunized mice had varying titers of sperm agglutinating antibodies. Nearly 40-50 per cent of the mice had a titre of 1:128 in both groups whereas only 33 per cent had sperm immobilizing antibodies. CMIR, as assessed by LMIT, was detected in immunized mice. However, this had not resulted in the infiltration of immune cells into the target organs perhaps due to the lower magnitude of immune response.

Effect of pregnancy plasma and monoclonal antibodies to HLA and DR antigens on leukocyte migration.

We studied the effect of pregnancy plasma and monoclonal antibodies to the histocompatibility antigens HLA and DR on migration of normal leukocytes from capillaries. It was observed that plasma from women in the first trimester of pregnancy significantly enhanced leukocyte migration at a concentration of 10% (mean area of migration = 50.7 +/- 9.2 cm2), as compared with plasma from nonpregnant women (22.8 +/- 7.0 cm2; p less than 0.05). This effect was less during the second trimester (39.5 +/- 3.5 cm2; p less than 0.05) and no enhancement was noted with plasma obtained from the third trimester of pregnancy. Similar results were obtained with a 20% concentration of plasma also. On the other hand, the monoclonal anti-HLA and anti-DR antibodies had an inhibitory effect on migration of leukocytes. These results are discussed in relation to the immunoregulatory role of pregnancy plasma in the nonrejection of the fetal allograft.

Multiple sclerosis: early prognostic guidelines.

To determine tentative early prognostic indicators in multiple sclerosis (MS), literature dealing with MS prognosis and rehabilitation, the records of University of Washington MS Clinic patients, and the opinions of directors of MS Clinics throughout the United States were reviewed. From a review of more than 200 books and articles, as well as MS clinic records, 13 indicators were identified. Characteristics reported as indicating a relatively good prognosis were: 35 years of age or less at onset, current ambulatory ability, monosymptomatic onset, sudden appearance of symptoms, initial remission within 1 month, most recent but less than 2 months, little or no residual deficit after each exacerbation, absence of extensor plantar reflexes and cerebellar signs at initial examination, optic neuritis or other sensory symptom as the sole presenting symptom, absence of initial motor symptoms and pyramidal and cerebellar signs minimal 5 years after onset. The 30 MS clinic directors responding to the survey felt that useful indicators, in order of their usefulness, were: current ambulatory ability, minimal pyramidal and cerebellar signs 5 years after onset, good remission of initial symptoms, prompt resolution of initial symptoms, age 35 or less at onset, only 1 symptom occurring during the 1st year, sudden appearance of initial symptoms, brief duration of the most recent exacerbation, and absence of cerebellar signs at initial examination. In addition to identifying tentative early prognostic indicators, this paper also outlines a simple method of quantifying the level of disability and outlines typical disease courses and rehabilitation service needs in MS.