GENERAL INTRODUCTION: RHABDOVIRIDAE

Introduction

Rabies (rabidus, L. = mad) is a highly fatal disease of humans and all other warm-blooded vertebrates, caused by a lyssavirus which is present in the saliva during the late stage of the disease and which is generally transmitted by the bite of diseased animals, most commonly dogs. From the bite wound the virus enters peripheral nerves and, during an incubation period of weeks to months, it spreads to the spinal cord and brain to produce a range of severe neurological clinical signs.

Rabies occurred widely in Europe, Asia and Africa throughout recorded history, but did not had a significant impact on human and livestock populations similar to diseases such as bubonic plague, smallpox, contagious bovine pleuropneumonia or rinderpest. Descriptions of the disease can be traced back further in early Chinese, Egyptian, Greek and Roman records than descriptions of any other infectious disease.^{252, 301} Controversy raged for centuries as to whether the disease arose spontaneously, or was caused by an agent transmitted by a bite, and it was not until 1804 that Zinke³⁰⁹  published a description of the experimental transmission of the disease to dogs and cats by brushing saliva from a rabid dog into wounds. Galtier¹⁰² described the transmission of the disease to a laboratory rabbit, and Pasteur soon thereafter established the  association of the causative agent of rabies with nerve tissue. He demonstrated by serial intracerebral passage of infected nerve tissue in laboratory animals that wild or ‘street virus’ could be transformed into ‘fixed virus’ with a shortened and reproducible incubation period.²⁰⁵ In a logical extension of their work, Pasteur and his associates reasoned that vaccine could be administered to humans after exposure to rabies virus to induce immunity before the infection became established in the victim. They 'attenuated’ the virus by desiccating strips of infected rabbit spinal cord over potassium hydroxide and administered suspensions of increasing ‘virulence’ to patients, starting with material dried for 14 days and ending with material dried for two days. The technique was first applied in 1885 on a nine-year-old boy, who survived, and within a short period the technique found widespread application and had a lasting impact on rabies immunization practices.²⁰³ Despite the development of a vaccine, the true nature of the infectious agent remained obscure and it was not until 1903 that Remlinger²¹³ demonstrated that it passed through filters that retained bacteria, and thus conformed to the newly defined group of agents known as viruses. In the same year, Negri¹⁹⁵ described the occurrence of cytoplasmic inclusions in infected nerve cells.

Aetiology

Viruses in the order Mononegavirales, family Rhabdoviridae (rhabdos, Gr. = rod), genus Lyssavirus cause rabies. The genus was initially divided into serotypes according to antigenic cross-reactivity and later genotypes based on genetic characterization. It is now delineated according to viral species based on several criteria including genetic distance, antigenic patterns in reaction with anti-nucleocapsid monoclonal antibodies and, where available, information on ecological properties such as host and geographic range.  Currently, 16 lyssavirus species are recognized by the International Committee on Taxonomy of Viruses (ICTV); comprising rabies lyssavirus, the type species and the other 15 species are referred to as rabies- related lyssaviruses^{3, 261} (Table 1). Two additional bat- associated viruses, Taiwan bat lyssavirus from Taiwan¹¹⁸ and Kotalahti bat lyssavirus from Finland²⁰¹ are not yet officially classified. Lyssavirus species are also divided into phylogroups I, II and III (Table 1) based on immunological and pathological characteristics.

Table 1 Lyssavirus species occurring worldwide