African Horse Sickness Virus: History, Transmission, and Current Status.

African horse sickness virus (AHSV) is a lethal arbovirus of equids that is transmitted between hosts primarily by biting midges of the genus Culicoides (Diptera: Ceratopogonidae). AHSV affects draft, thoroughbred, and companion horses and donkeys in Africa, Asia, and Europe. In this review, we examine the impact of AHSV critically and discuss entomological studies that have been conducted to improve understanding of its epidemiology and control. The transmission of AHSV remains a major research focus and we critically review studies that have implicated both Culicoides and other blood-feeding arthropods in this process. We explore AHSV both as an epidemic pathogen and within its endemic range as a barrier to development, an area of interest that has been underrepresented in studies of the virus to date. By discussing AHSV transmission in the African republics of South Africa and Senegal, we provide a more balanced view of the virus as a threat to equids in a diverse range of settings, thus leading to a discussion of key areas in which our knowledge of transmission could be improved. The use of entomological data to detect, predict and control AHSV is also examined, including reference to existing studies carried out during unprecedented outbreaks of bluetongue virus in Europe, an arbovirus of wild and domestic ruminants also transmitted by Culicoides.

African Horse Sickness Caused by Genome Reassortment and Reversion to Virulence of Live, Attenuated Vaccine Viruses, South Africa, 2004-2014.

African horse sickness (AHS) is a hemorrhagic viral fever of horses. It is the only equine disease for which the World Organization for Animal Health has introduced specific guidelines for member countries seeking official recognition of disease-free status. Since 1997, South Africa has maintained an AHS controlled area; however, sporadic outbreaks of AHS have occurred in this area. We compared the whole genome sequences of 39 AHS viruses (AHSVs) from field AHS cases to determine the source of 3 such outbreaks. Our analysis confirmed that individual outbreaks were caused by virulent revertants of AHSV type 1 live, attenuated vaccine (LAV) and reassortants with genome segments derived from AHSV types 1, 3, and 4 from a LAV used in South Africa. These findings show that despite effective protection of vaccinated horses, polyvalent LAV may, paradoxically, place susceptible horses at risk for AHS.

A comparison of the susceptibility of the biting midge Culicoides imicola to infection with recent and historical isolates of African horse sickness virus.

The susceptibility of Culicoides (Avaritia) imicola Kiefer (Diptera: Ceratopogonidae) to 21 isolates representing all nine known serotypes of African horse sickness virus (AHSV), recovered from clinical cases of the disease in South Africa during 1998-2004, was compared with its susceptibility to approximately 40-year-old isolates stored at the Agricultural Research Council-Onderstepoort Veterinary Institute. Field-collected C. imicola were fed through a chicken skin membrane on sheep blood spiked with one of the virus isolates to a concentration in the range of 5.6-7.5 log (10)TCID(50)/mL. After 10 days incubation at 23.5 degrees C, five of the nine historical serotypes (AHSV-1, -2, -3, -7 and -9) could not be isolated from C. imicola. All nine serotypes were recovered for the 21 recent isolates, for 16 of which the virus recovery rates were higher than for the corresponding historical isolates. These results emphasize the need to assess the oral susceptibility of local Culicoides populations to viruses in circulation during outbreaks in order to estimate their vector potential.

History of Orbivirus research in South Africa.

In the early colonial history of South Africa, horses played an important role, both in general transportation and in military operations. Frequent epidemics of African horsesickness (AHS) in the 18th century therefore severely affected the economy. The first scientific research on the disease was carried out by Alexander Edington (1892), the first government bacteriologist of the Cape Colony, who resolved the existing confusion that reigned and established its identity as a separate disease. Bluetongue (BT) was described for the first time by Duncan Hutcheon in 1880, although it was probably always endemic in wild ruminants and only became a problem when highly susceptible Merino sheep were introduced to the Cape in the late 18th century. The filterability of the AHS virus (AHSV) was demonstrated in 1900 by M'Fadyean in London, and that of the BT virus (BTV) in 1905 by Theiler at Onderstepoort, thus proving the viral nature of both agents. Theiler developed the first vaccines for both diseases at Onderstepoort. Both vaccines consisted of infective blood followed by hyper-immune serum, and were used for many years. Subsequent breakthroughs include the adaptation to propagation and attenuation in embryonated eggs in the case of BTV and in mouse brains for AHSV. This was followed by the discovery of multiple serotypes of both viruses, the transmission of both by Culicoides midges and their eventual replication in cell cultures. Molecular studies led to the discovery of the segmented double-stranded RNA genomes, thus proving their genetic relationship and leading to their classification in a genus called Orbivirus. Further work included the molecular cloning of the genes of all the serotypes of both viruses and clarification of their relationship to the viral proteins, which led to much improved diagnostic techniques and eventually to the development of a recombinant vaccine, which unfortunately has so far been unsuitable for mass production.

Veterinary immunology as colonial science: method and quantification in the investigation of horsesickness in South Africa, C. 1905-1945.

This article examines the practice of veterinary immunology in South Africa during the first half of the twentieth century through an analysis of research into a horsesickness vaccine at the Onderstepoort Veterinary Institute. From the early 1900s, Arnold Theiler prioritized research into horsesickness, by then defined as an insect-borne disease caused by an ultravisible virus. He succeeded in devising a means of prophylaxis using a simultaneous injection of infective blood and immune serum, but he discovered antigenically different strains of the virus, which could overcome the immunity produced by his treatment. The practical value of Theiler's methods was further limited by difficulties in standardizing the biological material used in immunization, the results of which remained too erratic for application on a large scale. No further advances were made until the 1930s, by which time Onderstepoort had been drawn more closely into international scientific networks. Using techniques derived from research into yellow fever in America and canine distemper in Britain, the Onderstepoort scientist Raymond Alexander invented a method of immunization that utilized the propagation of the horsesickness virus in the brains of mice. Alexander's methods, which were characterized by successful technical adaptation and innovation, depended upon methods of quantification first developed by Paul Ehrlich to standardize diphtheria antitoxin during the 1890s. During the 1940s, vaccination expanded rapidly in South Africa, and Onderstepoort later exported the vaccine and associated technology to other countries affected by horsesickness.

Possible spread of African horse sickness on the wind.

Analyses of outbreaks of African horse sickness showed that movement of infected Culicoides midges on the wind was most likely responsible for the spread of the disease over the sea from Morocco to Spain in 1966, from Turkey to Cyprus in 1960, and from Senegal to the Cape Verde Islands in 1943. The pattern of spread of the epidemic in the Middle East in 1960 could have been laid down by the infected midges carried on spells of south-east winds, and analyses of outbreaks in Algeria in 1965 and India in 1960 also suggested windborne spread of the disease. Each spread occurred when the presence of virus, host and vector coincided either with a spell of winds unusual for a particular time of year (Spain, Cyprus, Cape Verde Islands and Algeria) or with a series of disturbances usual at that time of the year (Middle East and India). Inferred flight endurance of the midge varied up to at least 20 h and flight range from 40 to 700 km. Flight occurred when temperatures were likely to have been in the range of 15-25 degrees C if it was at night or 20 to about 40 degrees C if it was by day.It is suggested that likely movements of midges on the wind can be estimated from synoptic weather charts, and should be taken into account when planning control of the disease in the face of an outbreak. Such control includes a ban on movement of horses, vaccination and spraying of insecticide.The risk of spread to countries outside the endemic areas should be assessed by reference to possible wind dispersal of infected midges.