Globally, rabies is the tenth leading cause of death due to infection in humans. The threat of rabies exists in most parts of the world (Figure-1). Predominantly, it affects poor people in developing countries and its true incidence may be underestimated. In the year 2005, there were reports estimating that nearly 60,000 human fatalities occur each year mostly in Asia and Africa (9). A WHO-sponsored multicentric study estimated that at least 20,000 deaths occurred annually in India alone (10). In China, rabies has, since May 2006, become the leading cause of infectious disease mortality, killing 3,293 people in 2006, 27% more than in 2005.
More than 99% of all human deaths from rabies occur in the developing world (11) and almost half of those dying of rabies and requiring rabies immunoglobulin are children less than 15 yrs old. The lack of supplies of rabies immunoglobulin and training in its correct use, condemns more than 55,000 people (90% conﬁ dence interval (CI) = 24,000-93,000) worldwide each year to die an agonizing death from rabies. Even this ﬁ gure underestimates the full burden of human suffering as millions of victims of potentially rabid bites suffer protracted anxiety resulting from the uncertain and sometimes very long incubation period of this infection (up to 6 years or more) (12). Deaths due to rabies are responsible for an estimated health burden of 1.74 million DALYs (‘Disability adjusted life years’) (90% CI = 0.75-2.93). Morbidity and mortality following side-effects of nervous-tissue vaccines account for an additional 0.04 million DALYs. The annual cost of rabies is estimated USD 583.5 million (90% CI = USD 540.1-626.3 million) in Asia and Africa alone (9).Assuming that 60% of post-exposure prophylaxis regimens require the administration of an average number of two vials of rabies immunoglobulin (dose according to body weight), the estimated annual requirements for this antiserum are: 1,200,000 vials for Africa, 350,000 for the Americas, 200,000 for East Mediterranean region, 4 million for the West Paciﬁ c, including China, and 3.2 million for South-East Asia, including India, thus resulting in a grand total need for approximately 9 million vials every year. These calculations are based on available epidemiological data that undoubtedly underestimate the size of the problem.
Snake bites and scorpion stings are well-known medical emergencies in many par ts of the world where these animals are distributed (Figure-3). Agricultural workers (the countries' food producers) and children are the most affected. The true worldwide incidence of snake bite envenoming has proved difﬁ cult to estimate. It has been reported that there are 5 million snake bites, resulting in 2.5 million envenomings, 125,000 deaths and perhaps three times that number of permanent sequelae in the world each year (13). The incidence of snake bite mortality is particularly high in Africa, Asia, Latin America and New Guinea. In India alone there may be as many as 50,000 snake bite deaths each year. Many estimates of snake bite mortality and resulting permanent morbidity are based on hospital returns, which greatly underestimate the real impact of this health problem, since most people affected by snake bites do not seek hospital treatment but prefer traditional remedies (14). Snake bite victims in rural areas may die at home unrecorded (15). A number of community-based studies have begun to disclose the true burden of snake bite mortality. For example, in the
Eastern Terai region of Nepal, there were 162 snake bite deaths per 100,000 population per year (16), and in a region of Nigeria, the incidence of snakebites was 497 per 100,000 people per year, with a fatality rate of 12.2% (17). A study performed in Malumfashi, Nigeria, showed that there were 40-50 snakebite cases, with 4 deaths per 100,000 population per year. Nineteen percent of those bitten developed persistent sequelae and only 8.5% sought hospital treatment (18) while in Kiliﬁ District in coastal Kenya, 68% of snake bite victims consulted a local muganga (“witch doctor”), only 27% went to hospital and 36% were left with permanent sequelae (19). Therefore, the actual impact of this neglected health problem on a global basis is much higher than has been previously realized. Analysis of the burden of human suffering attributable to these envenomings from a broader public health perspective reveals their greater impact. Evaluated using DALYs , the impact of envenomings is very high (estimated in 2 million DALYs per year for sub-Saharan Africa), because most victims are children or young agricultural workers, many of whom are left for the rest of their lives with permanent physical or psychological consequences of envenoming. The impact of snake bite as an occupational disease on the economy is also highly signiﬁ cant, as many of the affected people are agricultural workers (food producers) whose families, community and country are highly dependent on the products of their physical activity.
The true incidence of scorpion sting envenoming is not known because many cases do not seek medical attention. However, it has been estimated that there are approximately 1 million stings per year. In Mexico alone, 250,000 scorpion stings are reported yearly, but fatalities have declined from 2,000 to less than 50 per year following widespread distribu-tion of antivenoms. In Tunisia 40,000 stings, 1,000 hospital admissions and 100 deaths are reported each year. There is a high incidence in other parts of Northern Africa, the Middle East (notably Iran), India and Latin America. In Khuzestan, south-west Iran, where scorpion stings are the fourth leading cause of death, 12% of the 25,000 stings treated each year and more than 95% of the fatalities are attributable to Hemiscorpius lepturus (Hemiscorpiidae) (20). In Brazil, 37,000 scorpion stings and 50 deaths were reported in 2005 and, in this country, scorpion stings are an emergent health problem, due to the adaptation of some scorpion species to the urban environment.
THE NEED FOR THERAPEUTIC ANTISERA
On the basis of the epidemiological ﬁ gures presented above, the current annual need for antisera for post-exposure rabies prophylaxis and for the treatment of snake bite and scorpion sting envenomings amounts to 9 million vials of rabies immunoglobulin and 10 million vials of antivenoms. Unfortunately, the present worldwide production capacity is well below these needs. There are various reasons for this situation: governments and health authorities ignore antisera because of their neglected status; a number of private producers have stopped manufacture because of market instability and unproﬁ tability; the prices of some products are completely unaffordable by the health systems of developing countries; some former public manufacturers have been privatised, with a consequent drop in antiserum production because is perceived to be unproﬁ table. Furthermore, the weaken-ing of public health budgets has resulted in deterioration of infrastructure and equipment for antisera production in public institutions. This resulted in a global reduction in antisera production and accessibility. This trend should be reversed through concerted actions by national, regional and world health authorities and manufacturers.