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). There are no facilities or health personnel able to provide it in many areas where the disease is prevalent. A first approach to correct this problem would be by extending provision of modern PEP to areas where human rabies is most prevalent.

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. During this period an area of almost 1.9 million km² was targeted at least once with vaccine baits, with control taking between 5 and 26 years depending upon the country. We examined factors influencing effort required both to control and eliminate fox rabies as well as cost-related issues of these programmes. The proportion of land area ever affected by rabies and an index capturing the size and overlap of successive ORV campaigns were identified as factors having statistically significant effects on the number of campaigns required to both control and eliminate rabies. Repeat comprehensive campaigns that are wholly overlapping much more rapidly eliminate infection and are less costly in the long term. Disproportionally greater effort is required in the final phase of an ORV programme, with a median of 11 additional campaigns required to eliminate disease once incidence has been reduced by 90 per cent. If successive ORV campaigns span the entire affected area, rabies will be eliminated more rapidly than if campaigns are implemented in a less comprehensive manner, therefore reducing ORV expenditure in the longer term. These findings should help improve the planning and implementation of ORV programmes, and facilitate future decision-making by veterinary authorities and policy-makers.

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 <0.1 are broadly typical of rabies surveillance in endemic countries and areas without a history of rabies. Using outbreak simulation techniques we investigated how the probability of detection affects outbreak spread, and outcomes of response strategies such as time to control an outbreak, probability of elimination, and the certainty of declaring freedom from disease. Assuming realistically poor surveillance (probability of detection <0.1), we show that proactive mass dog vaccination is much more effective at controlling rabies and no more costly than campaigns that vaccinate in response to case detection. Control through proactive vaccination followed by 2 years of continuous monitoring and vaccination should be sufficient to guarantee elimination from an isolated area not subject to repeat introductions. We recommend that rabies control programmes ought to be able to maintain surveillance levels that detect at least 5% (and ideally 10%) of all cases to improve their prospects of eliminating rabies, and this can be achieved through greater intersectoral collaboration. Our approach illustrates how surveillance is critical for the control and elimination of diseases such as canine rabies and can provide minimum surveillance requirements and technical guidance for elimination programmes under a broad-range of circumstances.

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. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans.

Six criteria for rabies diagnosis in living dogs.

OBJECTIVE: The authors studied the predictive value of six criteria for clinical diagnosis of rabies in living dogs. DESIGN: Identify and test the criteria in a retrospective and prospective study. MATERIAL AND METHOD: Both studies were conducted at the Rabies Diagnostic Unit, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok. The authors reviewed 1,170 dogs that were kept under observation for 10 days after they exhibited abnormal behavior. To test the predictive value of the six criteria, a prospective study involving 450 rabies suspected dogs was also performed. RESULTS AND CONCLUSION: The six criteria demonstrated 90.2% sensitivity, 96.2% specificity and 94.6% accuracy for the clinical diagnosis of rabies. They can be used for a presumptive diagnosis and may help in prioritizing post-exposure treatments and institute urgent rabies control measures.

Survival of naturally infected rabid dogs and cats.

A total of 1820 dogs and 332 cats that appeared ill or had bitten humans or animals were observed for >or=10 days. Of these, 957 dogs and 94 cats that were confirmed to be rabid survived <10 days after admission to our institution. This study supports current recommendations that dogs and cats that are suspected of being rabid should be euthanized and examined or, if this is inappropriate, confined and observed for 10 days.

The rabies epidemic on Flores Island, Indonesia (1998-2003).

Flores is an isolated previously rabies-free Indonesian island which has been experiencing a canine rabies outbreak which resulted in at least 113 human deaths. It started with the importation of three dogs from rabies endemic Sulawesi in September of 1997. Local authorities responded with massive killing of dogs starting in early 1998. Approximately 70% of the dogs, in the district where rabies had been introduced, were killed during that year, yet canine rabies still exists on Flores at this time (June 2004). Approximately 50 percent of dog bite cases and human deaths were in children under 15 years of age. Between 1998 and the end of 2002, 3,389 post-exposure rabies treatments were provided and none of the treated subjects died. Almost all patients were given the Thai Red Cross intradermal rabies postexposure treatment regimen using tissue culture rabies vaccine. A small but unknown number of patients with very severe exposures also received equine rabies immune globulin. This occurrence indicates that even massive culling of the dog population, without an intensive vaccination campaign of the survivors, will not arrest an outbreak even if it occurs on a small island.