Rinderpest Virus

Introduction

Rinderpest, “cattle plague” in German, is the most devastating livestock disease in history. A virus, it presents quickly and has a high mortality rate. It infects all members of the artiodactyla order (even-toed ungulates). Believed to have originated in Asia, it spread east across Europe, then south through Africa. Out breaks throughout history have claimed hundreds of millions of cattle and undomesticated ruminants, leading to large-scale famines, economic loss, and ecological disturbances. Finally, after a global vaccination and eradication effort, rinderpest joined small pox as the only viruses to have been driven to extinction by humans.

Classification

Baltimore Classification: Group V
Family: Paramyxoviridae
Genus: Morbillivirus

Brief History

Evidence of rinderpest dates back to as early as 3,000 BCE in Egypt, based on records of its symptoms. It established in Europe by the fourth century with the Hun invasions, and out breaks have been documented throughout the Middle Ages. Fifteen outbreaks were reported in the fourteenth century across the continent. In the eighteenth century it claimed an estimate of more than 200,000,000 domesticated cattle (NY Times 1866).

Rinderpest returned to Africa in the nineteenth century with the Italian cattle imports from Yemen and India to Somalia. The first African epidemic began in 1887, and quickly spread and killed over 90% of the domestic and wild ruminant populations in Ethiopia, Kenya, the Sudan, and Uganda (Tambi et al. 1999). Several East African tribes, predominantly the Maasai, rely heavily on their cattle as a source of food, material, money, and status – a vital element of their culture. Rinderpest infects water buffalo, yaks, African buffalo, giraffes, elands, kudus, wildebeest, and Tragelaphine species of antelopes (Animal Health in the World), impacting ecosystems as well as human societies. The virus never established across the Atlantic Ocean, or in Australia.

Characteristics

Rinderpest virus (RPV) has been categorized as a Morbillivirus, a genus of Paramyxoviruses. It is closely related to canine distemper virus of dogs and big cats, the measles, peste-des-petits ruminants virus of goats and sheep, and the phocine distemper virus of seals. The virion has a spherical capsid and inner envelope, and a nonsegmented, negative sense single stranded RNA genome that codes for eight proteins, six structural (large, phosphoprotein, hemagglutinin, nucleoprotein, fusion, and membrane (Giavedoni)) and two non-structural. The virus’ surface proteins bind to receptors on susceptible cells, and the virion then fuses with the host cell, emptying its genetic content and own polymerase. The virus then immediately begins to replicate, and buds off new virions.

The virus moves quickly. It can be transmitted via direct contact, contaminated water, and through short distances in the air. It is not capable of vertical transmission (1). The virion can be easily deactivated by desiccation from heat and sunlight, however the close packing and herding of domestic cattle and the normal behavior of most the affected ruminants to herd aid in the virus’ transmission. The incubation lasts less than three weeks, with symptoms arising as soon as three days after infection. The virus targets the lymphatic system, and the epithelial cells in the respiratory system and gastrointestinal tract (Lund 2000). Early signs include high but short-term fever, depression, loss of appetite, and soreness along the gums. Nasal and ocular discharge follows, then by necrotic lesions in the mouth and gastrointestinal tract, bloody diarrhea, hemorrhaging, swollen lymph nodes, and dehydration. Death occurs in as early as ten days (1). An animal is contagious a few days before nasal and ocular discharge appears and all bodily fluids are infectious. During an epidemic, morbidity and mortality is between 80 to 100 percent.

Vaccine Development

Before a vaccine was developed, quarantine and euthanasia were the best solutions for controlling an outbreak. Early attempts at immunization started in the 1890s included injecting cattle with blood from an infected or recovered animal, (Bluesci), but this ran the risk of causing an infection. Walter Plowright developed the tissue culture rinderpest vaccine (TCRV), also called the Plowright tissue culture vaccine, in 1962. Plowright adapted Kabete “O” RPV, the most virulent strain, for culturing in calf kidney cells, and found that after ninety or more passages through the cells, the virus became nonpathogenic, and could be used for inoculation (Plowright). This is a classic method of formulating a live attenuated viral vaccine. RPV does not typically infect kidney tissue, but through repeat culturing in the medium, all virions in the new strain will target solely that target with reduced virulence. Exposure to the new strain prompts a rapid immune response before symptoms can begin, and the memory cells remain afterwards. Also, although the virus has an RNA genome, which typically mutate too quickly for an effective long-term vaccine, the RPV serotype, its surface proteins, has remained the same, even through the attenuation process. This trait means that a vaccine for one RPV strain is effective against them all, and grants life-long immunity.

However this vaccine has its drawbacks. The virion’s instability requires refrigeration, making it ineffective for vaccination programs in rural areas. Cattle also sometimes displayed moderate symptoms after inoculation. A heat-resistant recombinant vaccine was later developed in the 1980s using the virus’ surface proteins to generate an immune response. Vaccinia, the cowpox virus, is a typically asymptomatic virus with a broad host range and served as a vector for the small pox vaccine implemented in the pathogen’s eradication. Vaccinia has been designed to express RPV haemagglutinin (HA) and/or fusion (F) surface proteins to induce protective immunity. The hemogglutinin surface protein binds to host cell receptors and the fusion protein then aids in the spread of the virus to other cells (Giavedoni). Most vaccinia RPV vaccines use only the F surface protein, as it tends to elicit a stronger immune response and to be the most conserved (Yamanaka), but several vaccines use both. The mRNAs coding for the surface proteins first had to be cloned and synthesized as complementary DNA, as vaccinia has a double stranded DNA genome. Plasmid vectors then direct the cloning of these genes into the vaccinia genome, by introducing a transfer vector containing the genes for the RPV surface proteins spliced into a vaccinia plasmid, replacing several vaccinia genes, into a culture infected with normal vaccinia. The resulting recombinant vaccine provides life-long immunity equivalent to that of the tissue culture vaccine with only one inoculation.

Eradication

Multiple, still influential organizations arose to combat cattle plague. The first veterinary school opened in 1762 in France to educate its students on controlling the disease. The Office International des Epizooties, or the World Organization for Animal Health, was founded in 1924 to circumvent the difficulties of acting across international borders to control rinderpest. The Inter-African Bureau of Epizootic Diseases began in the first efforts to completely eradicate the virus in Africa in 1950. It enjoyed initial success using the early vaccines, but it ultimately failed to maintain its inertia and the pandemic resurfaced. The Pan-African Rinderpest Campaign commenced in 1986 with 35 participant countries with the goal of eradication, but also general pastoral education for improved livestock production and pasture protection. The campaign lead mass vaccination and surveillance programs for both domestic cattle and wildlife populations. While effective, this was only present in Africa, while the virus was still endemic in India and the Middle East. The Food and Agriculture Organization of the United Nations launched the Global Rinderpest Eradication Program in 1994 with the goal of a rinderpest free world by 2010. It succeeded. The last known case of rinderpest was in 2001 in Kenya, the last vaccinations were given in 2006, and the virus was declared extinct in the wild October 2010.