The Topic of This Month Vol.28 No.3(No.325)

Rabies as of 2006, Japan

(IASR 28: 61-62; March, 2007)

In November 2006, two cases of imported rabies occurred in succession after a 36-year absence (see p. 63 & 64 of this issue). Rabies is a zoonosis caused by rabies virus of the genus Lyssavirus of the Rhabdoviridae family, affecting all mammalians. However, the host animals affecting the continuation of the virus are restricted to the orders Carnivora and Chiroptera and all other species including humans serve as dead-end hosts.

Rabies case reports in Japan: In Japan, notification of rabies cases in compliance with the Communicable Diseases Prevention Law started in March 1947. In 1949, such a large number of rabies cases as 74 were reported. Owing to the enactment of the powerful Rabies Prevention Law in 1950, cases rapidly decreased after 1951, and with the last human and dog cases in 1956 and the cat case in 1957, eradication of rabies from Japan has been successful (Fig. 1). Since then, only an imported case of a returning traveler from Nepal who developed the disease in Japan in 1970 has been reported. Since April 1999, rabies has been a Category IV infectious disease in compliance with the Infectious Diseases Control Law and all physicians who have diagnosed rabies cases are obliged to report all cases (see p. 78 of this issue, and for the criteria of notification, see Two cases were reported in 2006.

Current status of rabies in the world: Rabies is still prevalent in India, China (see p. 68 of this issue), the Philippines (see p. 69 of this issue), and other Asian countries (see p. 66 of this issue); rabies-free countries in the world are extremely rare (Fig. 2). According to the re-evaluation made by WHO in 2004, deaths due to rabies in the world are estimated at 55,000 per year, most of them are in Asia (estimated at 31,000) or Africa (estimated at 24,000).

Postexposure prophylaxis of rabies: Owing to the long incubation period of rabies, almost complete protection of rabies is possible if postexposure prophylaxis (PEP) is implemented properly with vaccine and rabies immune globulin (see p. 75 & 76 of this issue). The population receiving PEP is estimated at 8-10 million per year. The economical burden for PEP is heavy, estimated at more than $500,000,000 in Asia. Several deaths are counted yearly in USA, and $300,000,000 is spent yearly for prevention of the disease. In poor countries, vaccines derived from nerve tissues are still used for PEP, and serious side effects occur in 0.3-0.8 individuals per population of 1,000. Tissue culture vaccines with low occurrence of side effects are expensive and the cost corresponds to the income of almost two months of an average African or that of about a month of an Asian. In developing countries, it is difficult to obtain human rabies immune globulin (HRIG), while equine rabies immune globulin (ERIG) is inexpensive, therefore ERIG is used principally. Since the main suppliers withdrew in 2001, obtaining even ERIG will possibly be difficult.

Problems on rabies control: Since safe and effective vaccine is available for rabies, its control is possible. As a result of insufficient surveillance, a high price of vaccine and immune globulin, and indifference of the government of developing countries, control or elimination has not been attained easily. For an infection of animal origin, 55,000 deaths rank the top, while rabies is the 12th in death number of infections in the world. Since there is no chance for a large-scale epidemic because of no human-to-human transmission, the priority tends to be lower than respiratory infections, diarrheal disease, AIDS, or tuberculosis. In surveillance performed in Tanzania, deaths due to rabies reported by the government was 0.04 deaths per population of 100,000, whereas those estimated by active epidemiological surveillance of dog-bite accidents were 4.9 per population of 100,000, indicating an underestimation of 1/100 (Cleaveland S, et al ., Bull WHO 80: 304-310, 2002).

Rabies control in endemic regions: More than 99% of human cases of rabies in developing countries are due to dog bite, and 90% of reasons for prescription of PEP are dogs. Anti-rabies policy in developing countries with rabies epidemics should, therefore, reside in control of dog rabies. In epidemics of rabies, killing dogs is one of the countermeasures, but population control only is not satisfactory because of high reproduction rate of dogs, and the result can be expected only by combination with vaccination program. Vaccination coverage is a matter of discussion in vaccination. The basic case reproduction number of infection, indicating spreading of rabies among dogs, R0, was estimated at 1.62-2.33 and the antibody coverage completely controlling epidemics should lie between 39-57% from pc =100 (1-1/R0) (Coleman PG and Dye C, Vaccine 14: 185-186, 1996). Therefore, coverage of 60% seems necessary to control rabies in an epidemic area. WHO recommends empirically higher than 70% vaccination coverage. In developing countries, it is said that 90% of dog population can access to humans; control of dog rabies is possible by vaccination of these dogs. In most developed countries, elimination of dog rabies has been in fact successful by this way. In North America and Europe, however, rabies virus has been maintained among wild animals, and for its control, oral vaccine administration using bait has been carried out. In Switzerland, France, Belgium, Luxemburg, and Czech, elimination of rabies from wild animals has been successful.

Defense against rabies importation into rabies-free countries: In such rabies-free countries as Japan, Australia, New Zealand and UK, the most important control method is prevention of invasion from overseas. The most effective method is quarantine of the importation of animals.

In UK, a new system PETS (Pets Travel Scheme) was introduced replacing the 180-day quarantine. This system allows importation of dog/cat from such countries with low risk of rabies without quarantine if certain conditions are met. At present, such countries have been expanded to USA and Canada and ferret has been added to the animal list. In such a system change, risk assessment is undertaken for a scientific ground. In Australia, exporting countries have been grouped into six categories, which set the quarantine period from 0 to 120 days depending upon the degree of risk.

In Japan, dog, cat, raccoon, fox, and skunk are subjected to import quarantine in compliance with the Rabies Prevention Law (see p. 79 and In addition to quarantine, registration and vaccination of dogs have been obliged to prevent domestic infection. In compliance with amendment of the Infectious Diseases Control Law, notification system has been required for the importation of mammals (see Because the notification form should be accompanied with a health certificate issued by the government authorities of the exporting country, the risk of importing rabies by animals may be on the marked decrease. While, if illegal importation of animals by smuggling or forgery of documents occurs, the risk will be on the considerable increase. Strict control of these activities seems important. Clinical veterinarians and public health veterinarians must recognize the presence of rabies in their daily activities (see p. 65 & 80 of this issue).

Conclusion: In view of more than 17 million overseas travelers every year, such a possibility can not be denied in future that those who have acquired infection in a foreign country develop symptoms after returning home. Providing necessary information to those who are visiting foreign epidemic countries is very important and also eradication of dog rabies in developing countries is important for the safety of Japanese travelers. The National Institute of Infectious Diseases is conducting laboratory tests of probable cases of rabies (see p. 70, 73, 81 & 83 of this issue).

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