During the past 13 years, the burden of human rabies in China increased, especially in 2001 and 2003, with a small drop in 2005 and 2008. Starting in 2001, China stopped producing the concentrated rabies vaccine for human use, and replaced it with the purified rabies vaccine, including the primary hamster kidney cell or vero cell-culture rabies vaccines . The price of the purified vaccine (156 RMB/person), was much higher than that of the previous concentrated vaccine (26 RMB/person). Some people exposed to rabies especially in rural areas were not vaccinated because they could not afford the expensive vaccine. This might be associated with the dramatic increase of human rabies incidence in 2001 [8, 9]. Although the atypical pneumonia pandemic in 2003 in China caught the attention of the world, in the same period the number of deaths due to rabies far exceeded those caused by atypical pneumonia. The huge number of resources directed to atypical pneumonia, which perhaps influenced the control and prevention of rabies at that time. The reason for rabies incidence decreasing in 2005 may be due to rabies control being emphasized and strengthened by local governments in some high prevalence provinces, such as Hunan and Guangxi . The rapidly and continuously increasing epidemic of rabies attracted the government of China, and a series of guidelines about rabies prevention were instituted and applied such as Technical Specifications of Rabies Control and Prevention in 2006 and Treatment Guidelines for Rabies Postexposure Prophylaxis of Humans in 2007, which maybe benefit the drop of rabies incidence in 2008.
Human rabies mainly distributed in the middle and southeast China and this distribution may be associated with the very high density of human populations and dog populations . The range of rabies-affected areas has been extending in China, and spreading to the west and north. This may be due to the gradual development of the transportation network, increased transportation of rabid dogs with people among different areas, and related economic factors. For example, as the economic condition is improving in China, more and more people can afford to own a dog, and any areas that had no human rabies reports have reported outbreaks of rabies since 1996, such as ZJJ city, Hunan province, where 34 rabies cases were reported in 2005 while there were no case reports in 1996 to 2004.
The rabies cases predominately occurred in the rural areas of the counties, which perhaps related to the larger numbers, more free-ranging existence, and lower vaccination rate in dogs, lack of knowledge about rabies and poor economic conditions [2, 12]. Affected populations were primarily farmers, children under 15 years old. The main seasons for rabies epidemics were summer and fall, when more frequent outdoor activities increased chance of human-rabid dog contact and exposure .
From the analysis of epidemiology characteristics of human rabies in recent years above, we know that China is now facing rabies outbreaks and the epidemic wave maybe relate to the change of rabies vaccine, application of related policies, and so on. To identify the more potential factors involved in the serious rabies emergence, we focused upon the three most seriously affected provinces, in which the two aspects of dogs and human PEP were analyzed in detail.
In China, dogs act as the main rabies virus infection source for human rabies . However, dog rabies surveillance often hasn't been carried out because the dog isn't an important economic animal in china. Insufficient data was obtained to fully address the relationship between the dog rabies and human rabies. In southern China, there are custom of eating dog meat, which make it possible that many brain specimens could be collected at the same time that dogs are slaughtered in local restaurants. In these brain specimens from apparently healthy domestic dogs, rabies positive samples were identified by DFA. In fact, not only in China but also in other countries, the reports about identification or isolation of rabies virus in apparently healthy dogs repeated [14–19]. Although no date are available concerning how long such dogs survive and no adequate evidence are provided, the phenomenon may be explained that rabies virus has reached the central nervous system before clinical signs appear rather than there are carrier or asymptomatic rabies state exists. About the dogs purchased by restaurants, they will be slaughtered soon and no time to transmit rabies virus to other dogs and humans but the butchers. Up to now, the dog meat consumers are considered no risk of rabies infection for no related reports appear. In our research, the rabies infection rate in dogs throughout the three provinces (2.3%) was relatively lower than other surveys (3.9% to 17.9%) in China [18, 19]. The discrepancies of infection rates is perhaps related to the sampling method (including the clinically suspicious rabid dogs or not), different sample sizes, detection methods, etc. Regardless of the infection rate, the data indicated that the disease in dogs prevailed in these regions, which represented an important cause of the high incidence of rabies in humans. But, there were no liner relationship between the rate of rabies infection in dogs and the incidence of human rabies, which illustrated that it was not the only factor influencing human rabies prevalence.
WHO has determined that vaccination coverage more than 70% is needed to sufficiently control canine rabies . In 2006, the estimated number of dogs in China was over 75,000,000. According to the statistical data of the local veterinary department, the vaccination rate of dogs in most areas investigated in this study was much lower than 70%, which is not favourable to rabies control. As suggested in previous studies, low dog vaccination rates is one of the major contributing factors for the rabies epidemic in the three provinces [13, 20, 21]. The vaccination coverage in dogs needs tremendous improvement.
Except the status of dogs influencing the epidemic of human rabies, PEP is another factor. We explored the category of rabies exposure in 711 cases in the three provinces. Of the cases investigated, 91.0% were attacked by dogs and 6.5% were attacked by cats. Most of these dogs haven't been vaccinated, and vaccination of cats is paid even less attention than that of dogs. In China, there are no official administrative rules concerning the animals attacking humans. In some areas, the dog would be killed after attacking humans, with few receiving observation and rabies detection. The status of animals after attacking humans was not always obtained.
According to WHO, as long as victims bitten by animals receive proper PEP, rabies can be prevented completely . In the 711 cases who died of rabies, 6.3% were classified category I contacts which should no risk of rabies. The phenomenon exposed a serious problem that some health care staff are not professional in rabies PEP. At the same time, the public ignorance of rabies should be notable, because 66.3% of victims did not seek medical services at all. 27.6% of the cases received inadequate PEP, which may contribute to the knowledge lack of rabies PEP of both medical staff and patients themselves. 6.0% of victims who had a full regime of PEP still died of rabies, may explained by the reduced quality of the vaccine due improper storage by the patients themselves after the first shot, as Han Si et al. analyzed . The investigation showed that the rate of wound treatment in the cases with category III exposure was higher than in those with category II exposure, and the rates of wound treatment and vaccination administration in those cases with head, face or neck exposures were all higher than in those with only limb exposures. This illustrated that with serious exposure at sites close to the head, the patients were more likely to seek medical service, and that lighter exposure more often was ignored. All these reflected that many people were not aware of the risk of rabies and always had aleatory ideas. Thus, publicity and education on risk and prevention of rabies is necessary and important to control epidemic, and should be strengthen in endemic areas, especially in rural areas.
Another reason for low rate of rabies PEP might be related to poor economic conditions. In China, human rabies mainly occurred in rural areas with slower economic development. In the rural areas of three high prevalence provinces in our study, the average annual net income per person was 2,496 RMB in 2005, while the total of the cost for PEP/person is about 1150 RMB (the lowest retail price of the rabies vaccine is 150 RMB/person, and the average cost for RIG is 1,000 RMB/person), accounting for 46.1% of the annual income. Patients exposed to rabies in China were estimated to be between 1% and 10% of the population, and several million persons are expected to require PEP each year at a minimum . To maximize efficiency of the limited subsidy and resource of human vaccines and rabies immunoglobulin for patients at real risk, PEP should be decided to initiate or withhold according to postmortem diagnosis of the biting animal. Therefore, establishing a systemic rabies diagnosis network is imperative. China government has aware of this problem, and some programs about rabies surveillance in animals especially in dogs have been carried out. It can be expected that reliable surveillance of dogs and aimed PEP service based on the diagnosis of the biting animal will effectively decreases the burden of human rabies epidemic.
In summary, only both animal rabies surveillance and control and human PEP are emphasized and strengthened at the same time, the serious human rabies epidemic in China at present could be effectively control, and the elimination of human rabies in China in the end will be possible.