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      Reemerging Rabies and Lack of Systemic Surveillance in People’s Republic of China

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          Abstract

          Standardized protocols and diagnostic-based surveillance are imperative for detection and elimination.

          Abstract

          Rabies is a reemerging disease in China. The high incidence of rabies leads to numerous concerns: a potential carrier-dog phenomenon, undocumented transmission of rabies virus from wildlife to dogs, counterfeit vaccines, vaccine mismatching, and seroconversion testing in patients after their completion of postexposure prophylaxis (PEP). These concerns are all scientifically arguable given a modern understanding of rabies. Rabies reemerges periodically in China because of high dog population density and low vaccination coverage in dogs. Mass vaccination campaigns rather than depopulation of dogs should be a long-term goal for rabies control. Seroconversion testing after vaccination is not necessary in either humans or animals. Human PEP should be initiated on the basis of diagnosis of biting animals. Reliable national systemic surveillance of rabies-related human deaths and of animal rabies prevalence is urgently needed. A laboratory diagnosis–based epidemiologic surveillance system can provide substantial information about disease transmission and effective prevention strategies.

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          Most cited references28

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          Infectious rabies viruses from cloned cDNA.

          The generation of infectious rabies virus (RV), a non-segmented negative-stranded RNA virus of the Rhabdoviridae family, entirely from cloned cDNA is described. Simultaneous intracellular expression of genetically marked full-length RV antigenome-like T7 RNA polymerase transcripts and RV N, P and L proteins from transfected plasmids resulted in formation of transcriptionally active nucleocapsids and subsequent assembly and budding of infectious rabies virions. In addition to authentic RV, two novel infectious RVs characterized by predicted transcription patterns were recovered from modified cDNA. Deletion of the entire non-translated pseudogene region, which is conserved in all naturally occurring RVs, did not impair propagation of the resulting virus in cell culture. This indicates that non-essential genetic material might be present in the genomes of non-segmented RNA viruses. The introduction of a functional extra cistron border into the genome of another virus resulted in the transcription of an additional polyadenylated mRNA containing pseudogene sequences. The possibility of manipulating the RV genome by recombinant DNA techniques using the described procedure--potentially applicable also for other negative-stranded viruses--greatly facilitates the investigation of RV genetics, virus-host interactions and rabies pathogenesis and provides a tool for the design of new generations of live vaccines.
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            Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

            These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.
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              Human Benefits of Animal Interventions for Zoonosis Control

              The economic aspects of controlling zoonoses are rapidly gaining attention in light of challenges, both well-known and new. Wildlife reservoirs of classical and emerging zoonoses (e.g., bovine tuberculosis) persist in many countries and substantially slow control efforts for livestock ( 1 ). The fast-growing demand for milk and meat in urban centers in resource-limited countries is leading to the intensification of livestock production systems, especially in periurban areas of these countries. However, because efficient zoonosis surveillance and food safety are lacking, the risk for zoonosis transmission is increasing, particularly in rapidly growing urban centers of resource-limited countries ( 2 , 3 ). Many countries in postcommunist transition face a sharp increase in zoonotic diseases resulting from the breakdown of government-run disease surveillance and control and weak private health and veterinary services ( 4 ). Industrialized countries have responded rapidly to recent zoonosis outbreaks and contained them well ( 5 ), but many resource-limited and transitioning countries have not been able to respond adequately because they lack human and financial resources and have not sufficiently adapted public health surveillance. In industrialized countries, an important part of successful zoonosis control has been compensating farmers for culled livestock. However, many resource-limited countries would not be able to conduct such programs. Most zoonoses are maintained in the animal reservoir but can cross over to humans as a result of different risk factors and behavioral traits. For example, brucellosis is transmitted to humans from direct contact with livestock or ingestion of unpasteurized milk or milk products; however, brucellosis is not transmitted from humans to livestock. Hence, elimination of zoonoses such as rabies, echinococcosis, and brucellosis is possible only by interventions that vigorously target animal reservoirs. Control of most zoonoses usually requires interventions outside the public health sector. When one considers health from a point of view independent of species, including humans, domestic animals, and wildlife, zoonoses are part of a broader ecologic concept of health systems ( 6 – 8 ). To attempt control, and possibly elimination, of zoonoses, benefits to public health and society need to be demonstrated, particularly in countries with scarce resources. We present examples from our work on brucellosis and rabies and demonstrate the circumstances for which zoonosis control would save money for resource-limited countries and likely reduce the occurrence of zoonoses worldwide. Avian influenza is discussed as an additional example. Diseases Brucellosis In Mongolia and central Asian countries after democratic reform and the shift from dependence on the former Soviet Union in 1990, human brucellosis reemerged as a major, but preventable, disease ( 9 ). After consultations with experts, the World Health Organization (WHO) raised the question whether mass vaccinations of animals saved money for the public health sector. We used an animal-to-human transmission model to estimate the economic benefit, cost-effectiveness, and distribution of benefit (to society and the public health and agricultural sectors) of mass brucellosis vaccination of cattle and small ruminants ( 10 ). The intervention consisted of a planned 10-year annual livestock mass vaccination campaign using Brucella melitensis Rev-1 for small ruminants and Brucella abortus S19 for cattle. In a scenario of achieving 52% reduction of brucellosis transmission between animals, 51,856 human brucellosis cases could be averted, which would add up to a gain of 49,027 human disability-adjusted life years (DALYs; see Appendix). The human death rate from brucellosis is considered to be 100,000 deaths for the United States alone ( 20 ). To implement disease prevention and control measures, early identification of emerging patterns of disease is necessary and uses economic methods to determine which mix of measures is most cost-effective. Resource-limited countries in Africa are almost devoid of surveillance capacity and efficient early warning systems, which would be crucial. Surveillance of cross-border diseases cannot be restricted to countries that have the funds. High-income countries would ultimately benefit by providing funding for surveillance and control to low-income countries. Comprehensive economic assessment of this issue are, however, lacking so far. Awareness, Knowledge, and Information Many countries, especially those with resource constraints and those in sub-Saharan Africa, lack information on the distribution of zoonotic diseases. Risks for zoonoses are considered negligible compared with those for diseases of higher consequence because the societal consequences of zoonoses are not recognized by the individual sectors. For example, outbreaks of Rift Valley fever in persons in Mauritania were mistakenly identified as yellow fever. The correct diagnosis was made only after public health services contacted livestock services, which informed them of abortions in cattle ( 21 ). In resource-limited and transitioning countries, many zoonoses are not controlled effectively because adequate policies and funding are lacking. However, transmission of zoonoses to humans can already be greatly reduced by health information and behavior. Authorities in Kyrgyz, for example, have started an information campaign to reduce brucellosis transmission to small-ruminant herders by encouraging them to wear gloves for lambing and to boil milk before consuming. Interventions in livestock should always be accompanied by mass information, education, and communication programs. Financing Substantial evidence documents that the combined effects of human disease caused by zoonoses, as part of the neglected infectious diseases, are in the same range as the classical diseases of poverty such as HIV/AIDS, tuberculosis, and malaria ( 22 , 23 ). On the other hand, the public health component justifies including zoonoses such as bovine tuberculoses in current global programs and initiatives on tuberculosis control ( 22 , 23 ). Recognition of these facts should result in affected countries applying for funds from the Global Fund to Fight AIDS, Tuberculosis and Malaria ( 24 ). Surveillance and control of cross-border zoonotic diseases such as highly pathogenic avian influenza cannot be restricted to wealthy countries. According to Vallat, “One country not able to carry out early detection and rapid response to animal disease outbreaks can represent a threat to all the others” ( 25 ). To approach these threats, new partnerships (e.g., between resource-limited and industrial countries, public and private sectors, and animal and public health) and permanent dialogue are needed. “It is evident that the interest of the rich countries is to support the others in order to protect themselves” ( 25 ). Zoonosis control in general should thus be seen from a global perspective and lead to a call for a global subsidiary approach for control. International bodies like the World Organization for Animal Health, the Food and Agriculture Organization, and WHO should foster establishment of global standards for zoonosis surveillance and control. Fostering of global standards is also part of the WHO International Health Regulations that will come into force in mid-2007 and will require all countries to do a better job of surveillance for diseases that can spread between countries (www.int/gb/edwha/pdf_files/WHA58-REC1/english/Resolutions.pdf). These efforts should lead to a global fund for the control of zoonoses or become a component of an extended Global Fund to Fight AIDS, Tuberculosis and Malaria. Such a joint facility would allow coherent and integrated control approaches, particularly in the countries with the most serious resources constraints, which in turn would benefit the whole world. Conclusion Zoonoses are among the most important animal and public health problems that affect the well-being of societies worldwide, yet they are too often forgotten or neglected. Because most zoonoses go unrecorded, they call for a rethinking of research and control efforts and the economic consequences. The example of brucellosis demonstrates that interventions in livestock against zoonoses, which would never be cost-effective when uniquely assessed from a public health sector point of view, may become cost-saving when considered from a societal perspective. Creating a new global finance facility for the control of zoonoses, similar to or linked with the Global Fund to Fight AIDS, Tuberculosis and Malaria, is timely, is of global interest, and represents a further contribution to successful attainment of the Millennium Development Goals.
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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                August 2009
                : 15
                : 8
                : 1159-1164
                Affiliations
                [1]Centers for Disease Control and Prevention, Atlanta, GA, USA (X. Wu, C.E. Rupprecht)
                [2]Academy of Military Medical Science, Changchun, People’s Republic of China (R. Hu)
                [3]Chinese Centers for Disease Control and Prevention, Beijing, China (Y. Zhang)
                [4]National Institute for the Control of Pharmaceutical and Biological Products, Beijing (G. Dong)
                Author notes
                Address for correspondence: Xianfu Wu, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G33, Atlanta, GA 30333, USA; email: xaw6@ 123456cdc.gov
                Article
                08-1426
                10.3201/eid1508.081426
                2815959
                19751575
                e28d8a46-4978-461d-b5c5-e80f6d795477
                History
                Categories
                Perspective

                Infectious disease & Microbiology
                vaccination coverage,rabies,perspective,viruses,postexposure prophylaxis,mass vaccination campaigns,china,carrier-dog phenomenon,seroconversion testing,counterfeit vaccines

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