The Extinction of Rabies?

Although canine rabies has been successfully eliminated from Western Europe and North America, someone in an undeveloped country dies from this horrible disease every ten minutes.  Because domestic dogs are the primary vector for the disease, understanding how rabies is transmitted among them in areas where the disease is still a problem is vitally important.

Fortunately, as reported in PLoS Biology, the unique pathology of the disease allowed a group of scientists to trace case-to-case transmission of the disease during an outbreak in Tanzania. They used this data analyze how the disease was transmitted between dogs and how it was transmitted from dogs to humans.

Rabies is a terrible disease. Not only do its victim suffer horribly, it also has the highest human fatality rate of all known infectious diseases. Every year approximately 55,000 people die of it and nearly all of these deaths occur in developing countries.  The disease is rarely seen in humans in Western Europe and North America where vaccination has successfully eliminated the disease from domestic dog populations.

Rabies is an acute viral encephalitis that is spread through the saliva of infected hosts. Clinical manifestations vary, but the neurological phase often includes increased aggression and the tendency to bite and thereby transmit infection; rapid progression to death is inevitable. These distinctive signs make transmission of rabies easier to track than that of most other diseases and provide an unusual opportunity to explore epidemiological patterns at the scale of the individual.

Transmission is the key factor in understanding the spread of infection.  Unfortunately, in the case of rabies, it has also been poorly understood.  At least until now.

The research team monitored the spread of infection by tracing contacts. This is where the odd symptoms of rabies proved to a benefit as the events that lead to transmission (typically a bite from an infected animal) were found to be both discrete and memorable. The team was able to record more than 3,000 potential transmission events between 2002 and 2006. Domestic dogs comprised more than 90% of their observations of rabid animals and were therefore considered to be the sole vector of rabies transmission to humans.

A bite from an infected animal is, of course, the primary way that rabies is transmitted. The biting behavior of dogs that were suspected to have rabies varied a lot with the mean number of bites per rabid dog being slightly more than two.  The probability that an unvaccinated dog would develop rabies after being bitten by an infected animal was approximately 50% (if it wasn’t killed or vaccinated immediately after being bitten).

While canine rabies vaccinate rates are far lower in Tanzania than they are in Western Europe or North America, several domestic dog vaccination campaigns were carried out in the area during the study period. The researchers found that no rabies outbreaks occurred when domestic dog vaccinate rates exceeded 70 percent. The most severe outbreaks occurred in villages where less than 20 percent of the dogs were vaccinated.

More than 300 vaccinated dogs were identified by contact tracing as having been bitten by rabid animals. Only ten of these animals showed any signs indicative of rabies, although in the absence of vaccination approximately 50% of these would have been expected to succumb to the disease. Individual actions by dog owners such as tying or killing exposed or infectious animals also had an impact.

Why weren’t vaccinations completely effective in preventing transmission of the disease?  Tanzanian dogs don’t receive the kind of care that our American dogs do. Because they suffer from poorer nutrition and more health problems they may not develop the same degree of immunity from vaccination that our dogs do. In undeveloped country other factors like failure to maintain vaccinations at proper temperatures, improper vaccination procedures and lack of tracking / registration information can also adversely affect the effectiveness of vaccines.

With the goal of determining what percentage of the domestic dog population needed to be vaccinated to prevent rabies outbreaks, the team set out to collect data. Their goals were: to understand the transmission dynamics of rabies in domestic dog populations; to understand the demographics of domestic dog populations in Tanzania; and to collect information about the practicality and effectiveness of vaccination.

Their data showed that demographics of the local dog population appear to be a controlling factor on the percentage of animals that need to be vaccinated to control rabies transmission.

When vaccinations are carried out in pulses, births and deaths within the host population will continuously reduce the level of herd immunity attained during campaigns. Turnover of domestic dogs in rural Tanzania is very high; therefore, annual campaigns should aim to vaccinate 60% of the dog population to maintain vaccination coverage above [critical levels] for the duration of the interval between campaigns. When successive campaigns have achieved this, rabies incidence has declined dramatically despite high endemic levels in adjacent areas. Domestic dog population turnover therefore appears to have had a marked influence on rabies dynamics that explains the variable success of vaccination efforts.

They calculated that if 70 percent of the domestic dogs were vaccinated, rabies could effectively be eliminated from human and domestic dog populations.  Vaccination of all dogs is not a feasible goal in undeveloped areas like rural Tanzania but 70 percent coverage may be an achievable goal, even in areas where canine birth and death rates are high.

The problem of canine rabies has often been considered intractable in rural Africa, because of poor infrastructure, limited capacity, and the misperception that large populations of wild carnivores are responsible for disease persistence. Our analyses show that global control of canine rabies is entirely feasible and that successful elimination of canine rabies in many parts of the world has likely been achieved precisely because R₀ is so low and institutional commitment to maintain high levels of vaccination coverage has been sustained. Achieving vaccination coverage of 60% or more in dog populations in Africa is both logistically and economically feasible through annual vaccination campaigns. The resultant reduction in costs of human post-exposure prophylaxis suggests that vaccination interventions targeted at domestic dog populations could translate into appreciable savings for the public health sector.

It would be wonderful if vaccination programs could make rabies as rare as polio or smallpox. The beauty of a program like the one proposed here is that it doesn’t rely on new, or even advanced, technologies. And the cost (in dollars, and more importantly – in lives) of an appropriately designed, sustained domestic dog vaccination campaign, will absolutely be less than the costs we’ll pay if we don’t do it.

Instant Rabies Test — Too Good to be True?

A mea culpa:

Last week I posted about Dyne Immune’s new saliva test for rabies. I checked out what folks in the veterinary community were saying about it. Based on the information I found (and on previous field experience where I used immunoassay tests to screen for contaminants), I wrote a story about how the new test combined with recent advances in treatment might make a difference for people in less developed countries where rabies is still a significant threat.

According to my friend Terrierman, there is more to this than the sunshine and bunnies in the press release. And — sadly — I suspect he’s right.

Read the rest here

New Advances in Rabies Testing and Treatment

IMPORTANT UPDATE FEBRUARY 18, 2009: After reading Pat the Terrierman’s excellent bit of investigative reporting we have serious questions regarding Dyne Immune LLC and the Rabies RAPID test. Please go here for more.

Please note that our skepticism does not extend to GreenPharm and Rabivir.

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Today MSNBC reports that Dyne Immune, LLC has released a portable rabies antigen test. The Rabies RAPID(TM) (Rapid Antibody Portable Immunodetection) Screen can reportedly detect the presence of rabies in a saliva sample in 30 minutes.

The test is quicker and far less invasive than the direct fluorescent antibody test (dFA) used since the 1960’s  to diagnose rabies in animals. The rabies virus lives in nervous tissue, not blood, so the dFA test is conducted on brain tissue. The test is performed after the animal is dead by putting fluorescently tagged rabies antibodies into the brain tissue sample. The antibodies will bind to any rabies virus antigens  present and allow them to be viewed with a fluorescent microscope.

The Rabies RAPID (TM) Screen provides results much more quickly and inexpensively than dFA testing and will also provide animal care professionals with a way to test for rabies in living animals.

“This test can reduce the number of animals destroyed and save doctors and animal control organizations from the costs associated with traditional testing,” said Dyne Immune CEO, Dr. V. James DeFranco, MD. “Most importantly, though, it enables them to screen for rabies and get an answer quickly — and that’s essential when it comes to preventing the infection from spreading.”

Rabies RAPID(TM) Screen detects the virus’ antigen in saliva and indicates a positive result in the low microgram-per-milliliter range. A simple results window in the screening kit indicates within minutes whether an animal is infected with rabies. The test is packaged in a small, lightweight kit that can be used both in the field and in the lab as a primary screening tool. 

According to the World Health Organization rabies continues to be a significant health problem in many parts of Asia and Africa. Most of the more than 55,000 human deaths each year occur among children in these parts of the world. Patients in less developed countries aren’t typically able to receive preventative rabies immunoglobulin treatment due to its high price and continuing global shortages.

There is no recognized successful medical treatment for clincial rabies, though the “Milwaukee Protocol” has now saved a few victims. Most victims of the disease die a horrible death in their homes and many of these cases are never officially diagnosed or reported. An inexpensive, rapid, accurate way to test animals for the disease might help prevent some of these deaths.

It appears that while the test is commercially available it is still in the beta test process. The company includes the disclaimer: “A negative result does not guarantee that rabies is not present,” on their website. They are currently soliciting qualified professionals to try and evaluate the test, free of charge.

In other rabies-related news, last month scientists at the South African company GreenPharm won an award  for work that may lead to safer, cheaper treatment for people bitten or scratched by rabid animals. As noted above, the high cost of rabies antibodies makes them difficult to obtain in developing countries. GreenPharm is using genetically modified tobacco to produce the rabies antibody drug Rabivir. Company representative say that not only will Rabivir be less expensive than traditional antibody treatments, it will also be safer. The rabies antibody drugs now used are derived from human or equine antibodies which can be contaminated with potentially fatal pathogens such as hepatitis, “especially in Africa where serious blood-borne infectious diseases are prevalent”.

The drug is still in the animal testing phase. We hope it meets expectations. The combination of quick, inexpensive screening and affordable antibody treatment could help make the heart-breakingly high number of people who die of rabies each year a thing of the past.

The Ormskirk Medicine

Rabies has long been one of the most dreaded diseases — before the advent of vaccination — it was fatal to all who contracted it.  The Manchester Evening News reports on an interesting bit of rabies-related history:

A REMEDY used to treat dog bite victims on the streets of Manchester in the Victorian era has been rediscovered by historians.

The city streets were once teeming with stray dogs – and one bite from a rabid animal could end in fatal illness.

A number of home-spun remedies were in widespread use throughout Britain before an effective vaccine was created by French scientist Louis Pasteur.

Science historians at the University of Manchester have now uncovered the recipe for one such treatment – known as the Ormskirk Medicine after the town from where it originated – and believe it shows surprising sophistication.

How sophisticated was it?

Dr Emm Barnes, from the Centre for the History of Science, Technology and Medicine, said: “The medicine would not have cured or prevented rabies but it shows quite a sophisticated knowledge of medicine and would have helped treat the wound. The active ingredients in the medicine were aniseed which is a mild antiseptic and a herb called horseheal which is still used by vets today, as well as alum which helps blood clot.

“The mixture would be mixed with vinegar, which is also an antiseptic, and soaked on bandages which would be applied to the skin.

“Pasteur’s new treatment was controversial because it was only the second vaccine ever invented. People still used the Ormskirk Medicine for quite a few years afterwards until it became clear that the vaccine was preventing rabies.”

The first recorded use of  the Ormskirk Medicine pre-dated Pasteur’s treatment by about a century. But — it seems that even before Pasteur first treated a person for rabies in 1885, the Ormskirk Medicine was seen as controversial.  In 1830, T.B. Johnson published his Hunting Directory; Containing A Compendius View of The Ancient and Modern Systems of The Chase.  The book includes a lengthy chapter on The Hydrophobia in which the author discusses dog bites, disease transmission and a biting critique of the Ormskirk Medicine:

The hydrophobia affords a striking instance of successful quackery in the avidity with which the Ormskirk Medicine was purchased, till within these few years that the imposture has been exposed. This compound of calcined oyster shells, elecampane, roach alum, and bole ammoniac, was originally administered gratis ; but no sooner was it discovered that the medicine was eagerly sought after, than the sale of it was advertised ; agents were appointed in different parts ; and many hundreds purchased and took the medicine who had been bitten, but not by mad dogs. A dog accustomed to the country, is generally alarmed when he approaches a town or village — the shaking of a cobler’s apron, or some such thing, is frequently resorted to by the lower orders — the terrified animal takes to his heels, and will most likely snap at any person who attempts to impede his progress.

Nothing is heard but the cry of mad dog ! and many who have been bitten under such circumstances, have called in the assistance of the Ormskirk medicine, and have thus been willing to suppose a disorder prevented, which did not exist in the dog, and which, of course, could not be communicated.

The venders of the Ormskirk medicine, however, made the most of the matter — its infallibility magnified upon the public in the most barefaced manner ; and it was even publicly stated, that such was the virtue of the medicine, that even after the hydrophobia had made its appearance, the disease could be removed by taking it.

Cases, with fictitious names, were stated, and the grossest falsehoods resorted to, in order to levy contributions with more plausibility upon the credulity of the unthinking. I believe, at present, no person who wishes to preserve even an appearance of character, will attempt to palm the medicine upon the world ; but it has still its supporters, and a number of old women, in various parts of Lancashire, still practice the deception ; and shew considerable dexterity in propping its falling reputation.

The recipe was obtained by the late Mr. Hill’s father, who resided near Ormskirk, from an itinerant tinker, in the year 1704. The medicine is thus prepared : — take one tea spoonful of prepared (calcined) oyster shells, one knife point full of roach alum, as much elecampane, in powder, and half a tea spoonful of bole ammoniac ; all to be powdered finely, and given to the patient in the morning fasting, in a little wine and water, or small beer : at the same time the wound is to be dressed with a preparation, varying from that just described, only in a greater portion of roach alum.

Not one dog in twenty, reputed mad, is so in reality — the cure, or rather the prevention, therefore, is certain in many instances ; and where it happens otherwise, and the dog was labouring under the hydrophobia, the result is most melancholy : but then it is immediately and unblushingly asserted, that the medicine had not operated in a proper manner — it had not remained upon the stomach, or been taken in sufficient quantity ; and thus the cheat continues, though on a much more circumscribed scale.

The fact is, that the only certain remedy hitherto discovered for this dreadful disease, is the application of the knife : — the blood becomes infected by the saliva from the dog’s teeth ; and unless the bitten part can be immediately cut out, death will most likely be the result, though the precise time will be very uncertain ; for so capricious is this malady, that, after infection, it sometimes lies dormant, as it were, in the system for months, sometimes for weeks ; while instances, I believe, are not wanting, where it has appeared, in all its terrible symptoms in the course of a few days.

It is possible that a person might be bitten by a mad dog, and yet escape the hydrophobia : if, in the act of biting, the animal’s teeth pass through a thick woollen coat, or other garment, so that his teeth in passing through are wiped dry, he might inflict a wound without any of the infectious saliva or fluid reaching it.

Johnson’s treatise not only presents a scathing indictment of the Ormskirk Medicine, it also provides an interesting discussion on dog bites and – rightly – points out that not all dogs that bite are rabid and not all bites from rabid animals will necessarily result in disease transmission.  But — please note that any time you are bitten by an animal you must either find out it’s rabies status – or undergo treatment.  Remember, with only very rare exceptions — rabies kills everyone who contracts it.

Other treatments used in before Pasteur’s vaccine included: filing the teeth of possibly infected animals down so that they couldn’t bite, herbal treatments including Mad-dog skullcap, cauterisation and excision of bite wounds, vapour baths, sucking the wound, applying caustic treatments and following various rituals including ‘hair of the dog*’.  One doctor even advocated spanking the disease out of a victim. 
 
* “Hair of the dog” originally referred to applying the hair of the dog that bit you to the wound; or to eating it’s hair, heart or liver on the principle that ‘like cures like’.