Global rabies management: perspectives on regional strategies for prevention and control.

Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir.

Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii.

Priorities in applied research to ensure programmatic success in the global elimination of canine rabies.

The elimination of human rabies mediated by dogs is attainable in concept, based upon current sensitive and specific diagnostic methods, existing safe and effective human and veterinary vaccines and a sound virological, pathological and epidemiological understanding of the disease. Globally, all developed countries achieved this goal. Regionally, major progress occurred throughout the Americas.

Correction to: Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

The original article [1] contained an error in the Author details paragraph. "Neglected Zoonotic Diseases, World Health Organization, Geneva, Switzerland" should be replaced by "Le Grand-Saconnex, Switzerland".

Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

The mass vaccination of dogs is a proven tool for rabies prevention. Besides parenteral delivery of inactivated vaccines, over the past several decades, several self-replicating biologics, including modified-live, attenuated and recombinant viruses, have been evaluated for the oral vaccination of dogs against rabies. Vaccines are included within an attractive bait for oral consumption by free-ranging dogs.

Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania.

A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project.

Lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies.

Lyssaviruses are bullet-shaped, single-stranded, negative-sense RNA viruses and the causative agents of the ancient zoonosis rabies. Africa is the likely home to the ancestors of taxa residing within the Genus , Family . Diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years.

Worldwide rabies deaths prevention--A focus on the current inadequacies in postexposure prophylaxis of animal bite victims.

The World Health Organization reports that over 60,000 humans die of rabies annually, worldwide. Most occur in remote regions of developing countries. Almost all victims received no postexposure rabies prophylaxis (PEP).

Customized online and onsite training for rabies-control officers.

Problem: It is difficult to deliver adequate training for people working in rabies control in low and middle-income countries. Popular e-learning systems for low-income settings are not well suited to developing and testing practical skills, including laboratory methods.

Approach: We customized training in rabies control methods for African professionals and students from different disciplines.

Estimating the global burden of endemic canine rabies.

Background: Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.

Methodology/principal Findings: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework.

The changing landscape of rabies epidemiology and control.

Over the past 20 years, major progress has been made in our understanding of critical aspects of rabies epidemiology and control. This paper presents results of recent research, highlighting methodological advances that have been applied to burden of disease studies, rabies epidemiological modelling and rabies surveillance. These results contribute new insights and understanding with regard to the epidemiology of rabies and help to counteract misperceptions that currently hamper rabies control efforts in Africa.

The elimination of fox rabies from Europe: determinants of success and lessons for the future.

Despite perceived challenges to controlling an infectious disease in wildlife, oral rabies vaccination (ORV) of foxes has proved a remarkably successful tool and a prime example of a sophisticated strategy to eliminate disease from wildlife reservoirs. During the past three decades, the implementation of ORV programmes in 24 countries has led to the elimination of fox-mediated rabies from vast areas of Western and Central Europe. In this study, we evaluated the efficiency of 22 European ORV programmes between 1978 and 2010.

Eliminating canine rabies, the principal source of human infection: what will it take?

More than 50,000 people die of rabies each year; most are children in developing countries, and almost all have been bitten by dogs. Eliminating canine rabies throughout the world would save thousands of lives and would reduce the economic impact of the disease by dramatically reducing the requirement for postexposure prophylaxis (PEP). Lengthy experience in the industrialized countries and ongoing programs in Latin America, Africa, and Asia have shown that the elimination of rabies in dogs is an achievable goal.

Surveillance guidelines for disease elimination: a case study of canine rabies.

Surveillance is a critical component of disease control programmes but is often poorly resourced, particularly in developing countries lacking good infrastructure and especially for zoonoses which require combined veterinary and medical capacity and collaboration. Here we examine how successful control, and ultimately disease elimination, depends on effective surveillance. We estimated that detection probabilities of <0.

Diketopyrrolopyrrole-porphyrin conjugates as broadly absorbing sensitizers for dye-sensitized solar cells.

A series of four new push-pull zinc porphyrin-based dyes was synthesised for hybrid photovoltaic solar cells with a view to enhancing the light-harvesting efficiency at approximately 550 nm with a diketopyrrolopyrrole (DPP) unit. The strength of the donor side of the push-pull porphyrin was tuned by affixing the electron-rich 4,4'-dimethoxydiphenylamine group at the meso position of the macrocycle, and the influence of the distance between the semiconductor surface and the porphyrin chromophore was assessed by introducing different π-conjugated spacers. Charge-transfer transitions over great distances were characterised by electronic absorption spectroscopy and DFT calculations.

Renewed global partnerships and redesigned roadmaps for rabies prevention and control.

Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this "incurable wound" persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector.

Zoonoses and marginalised infectious diseases of poverty: where do we stand?

Despite growing awareness of the importance of controlling neglected tropical diseases as a contribution to poverty alleviation and achieving the Millennium Development Goals, there is a need to up-scale programmes to achieve wider public health benefits. This implementation deficit is attributable to several factors but one often overlooked is the specific difficulty in tackling diseases that involve both people and animals - the zoonoses. A Disease Reference Group on Zoonoses and Marginalised Infectious Diseases (DRG6) was convened by the Special Programme for Research and Training in Tropical Diseases (TDR), a programme executed by the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO.

Animal health in the 21st century-a global challenge.

On the occasion of the centenary of the Friedrich-Loeffler-Institut, a conference entitled 'Animal Health in the 21st Century' was held in Greifswald, Germany, on 11-13 October 2010 to discuss current and future challenges regarding the global situation regarding infectious animal diseases and zoonoses, animal breeding, animal nutrition and animal welfare. Particular attention was paid to the impact of recent developments and anticipated future trends on livestock production.

hSMG-1 is a granzyme B-associated stress-responsive protein kinase.

Granzyme B plays a key role in cell-mediated programmed cell death. We previously demonstrated that p53 is a functional determinant in the granzyme B-induced cytotoxic T-lymphocyte response. However, the pathways leading to activation of p53 by granzyme B remain incompletely understood.

Immune surveillance of human cancer: if the cytotoxic T-lymphocytes play the music, does the tumoral system call the tune?

Accumulating evidence indicates that the innate and adaptive immune systems participate in the recognition and destruction of cancer cells by a process known as cancer immunosurveillance. Tumor antigen-specific cytotoxic T-lymphocytes (CTL) are the major effectors in the immune response against tumor cells. The identification of tumor-associated antigen (TAA) recognized primarily by CD 8(+) T-lymphocytes has led to the development of several vaccination strategies that induce or potentiate specific immune responses.

Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans.

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP.

ICAM-1 has a critical role in the regulation of metastatic melanoma tumor susceptibility to CTL lysis by interfering with PI3K/AKT pathway.

Human primary melanoma cells (T1) were found to be more susceptible to lysis by a Melan-A/MART-1-specific CTL clone (LT12) than their metastatic derivative (G1). We show that this differential susceptibility does not involve antigen presentation by target cells, synapse formation between the metastatic target and CTL clone, or subsequent granzyme B (GrB) polarization. Although PI-9, an inhibitor of GrB, was found to be overexpressed in metastatic G1 cells, knockdown of the PI-9 gene did not result in the attenuation of G1 resistance to CTL-induced killing.

Tumor resistance to specific lysis: a major hurdle for successful immunotherapy of cancer.

Research over the past decade in tumor immunology has shown that immune reactivity to tumor antigens can decrease tumor growth in experimental models. These observations have been translated into clinical studies involving both passive and active forms of immunotherapy. Immunotherapy, an alternative treatment for cancer, is confronted to a major hurdle: tumor escape of specific lysis.