CASE NOTES


BLUETONGUE VIRUSES—THE CURRENT SITUATION IN AUSTRALIA AND BEYOND

PD Kirkland, Virology Laboratory, EMAI, Camden NSW

Posted Flock & Herd April 2013

BACKGROUND

Bluetongue viruses (BTV) have been known for more than a century and from time to time have been a cause of major disease outbreaks. Viruses belonging to the bluetongue group are almost exclusively vector borne, with biological transmission by biting midges of the Culicoides genus. Until recently, the global distribution of the competent vector species was considered to be limited mostly to tropical/subtropical and warm temperate regions. Virus transmission is usually confined to the summer and autumn months (or the equivalent time periods), even in the tropical regions where distinct seasons are less apparent.

OCCURRENCE OF DISEASE

The most recent large scale epizootic with a high morbidity and mortality occurred on a number of the Mediterranean Islands and later in most of the countries bordering the northern Mediterranean coast between 1999 and 2002. In Italy and Sicily alone, as most if not all of the livestock population was highly susceptible, more than 500,000 sheep were affected. Disease is almost exclusively confined to sheep, though some highly virulent strains occasionally cause disease in goats. There was no evidence of disease in cattle until the emergence of an unusual strain of BTV serotype 8 (BTV-8) in The Netherlands and Germany in 2006, with subsequent spread through most of Western Europe and into England and southern parts of the Scandinavian countries. This strain of BTV-8 has characteristics of a cell culture adapted strain of virus, which include the capacity to cross the placenta in ruminants, cause congenital defects and to be excreted in semen. It also caused mild disease in a very small proportion of infected cattle. However, cattle are generally considered to be the amplifying mammalian host and can carry infectious virus for many weeks, long after the development of an antibody response.

Although BTVs can cause significant economic loss in some sheep populations, by far the greatest economic impact is through trade restrictions. This is currently the sole area of concern in Australia - in some cases market access is completely prevented while in others the losses result from costs associated with pre-export quarantine and testing.

VIRUS CHARACTERISTICS

Antigenically different strains of BTV have been classified on the basis of differences in neutralisation with reference antisera and have been grouped into serotypes. This classification however has limitations because there is no consistent relationship between serotype and virulence. At the host level, following natural infection there is strong immunity against re-infection of viruses within the same serotype and limited or no cross protection following infection with a heterologous serotype. The characterisation of viruses into serotypes also clearly has relevance to the development of vaccines. There are now 26 recognised serotypes, but with the widespread use of sensitive technology such as real time PCR, it is likely that additional serotypes that have been difficult to culture will be discovered.

Not all serotypes are globally distributed nor are they found with similar frequency within a region. Some serotypes have been discovered and then not detected again for many years whereas others are detected almost annually. Within a serotype, there can be considerable variation in virulence- usually in different geographical areas but sometimes within the same region. Some strains can be sufficiently virulent to cause a high morbidity rate (>50%) and a similarly high case fatality rate whereas others do not cause any detectable clinical signs, even under controlled conditions with close observation.

EPIDEMIOLOGY

The distribution and seasonal occurrence of BTVs is determined solely by the presence of competent Culicoides. Most Culicoides are very susceptible to cold weather and populations decline rapidly with the onset of cold weather and in temperate regions, become extinct with the first frost. Small pockets of insects may survive in mild coastal regions. In tropical regions, peak populations are also found in the warmer moist months, though excesses of either rainfall or temperature can limit or reduce populations. An exception has been found following the recognition of several species (especially those belonging to the C. obsoletus/pulicaris complex and C. dewulfi) in the northern hemisphere that are relatively tolerant to cold conditions and also have a capacity to survive indoors in barns and stables. In the warmer months, these insects have a range extending from the Mediterranean to well north of the Arctic Circle. It is believed that higher temperatures that occurred in 2006 enabled more efficient virus replication, allowing BTV to become established in species that were previously not known to be susceptible. Once the virus was present, high attack rates on highly susceptible ruminant populations resulted in rapid and widespread virus transmission. The capacity of these midges to survive through cold conditions has provided a mechanism for overwintering of viruses (including the recently discovered orthobunyavirus, Schmallenberg) in some locations.

Bluetongue viruses are transmitted with poor efficiency compared to some Culicoides-borne viruses (eg Akabane), mostly because of the very small proportion of the vector population that is capable of being infected, often less than 1%. Within a vector species, a high proportion of the population is often refractory to infection. However, at the peak of a transmission season, cattle can be attacked by >50,000 midges in a short period, offsetting some of the low infection rates in the population. In areas where vectors and BTV are abundant, a prevalence (and incidence) of >90% in cattle is not uncommon. However in most situations infection of sheep does not occur or the incidence is very low until there are conditions that support a high level of transmission in cattle, probably allowing 'spill-over' into sheep to occur.

CURRENT AUSTRALIAN SITUATION

In Australia, there are currently 10 serotypes of BTV (1, 2, 3, 7, 9, 15, 16, 20, 21 and 23). Serotypes 2 and 7 are recent introductions and have been discovered in the last 5 years. Serotypes 1 and 21 remain widely distributed throughout the vector range and are the only serotypes that have been found in NSW. Until recently, all other serotypes were confined to a relatively small area in the far north of the NT and WA. However, in 2010, BTV2 was detected in several locations in both north and central Queensland and in 2011 and 2012 other serotypes (probably 15 and 23) have been detected on Cape York. It is thought that BTV2 may have been introduced to Qld with the movement of viraemic cattle from the NT during the vector season. It has not been detected since 2010 and may not have persisted. Based on molecular analyses, the incursions in the far north on Cape York and near Townsville are probably the result of 'dumping' of infected midges from Indonesia and PNG under cyclonic conditions though it is also possible that similar conditions may have spread insects from the NT. Modelling studies have recently shown that under conditions that allow midge survival, insects can be transported from Indonesia to northern Australia in about 24 hours. In addition to the detection of new serotypes, nucleic acid sequencing of isolates of previously recognised serotypes have identified the presence of new strains containing virus genome segments (BTVs have 10 separate RNA segments) only previously identified in Indonesia.

Some of the Australian serotypes (especially 16 and 23) have been shown under experimental conditions or following movement of sheep to the NT, to be moderately pathogenic. Mortality rates up to 40% have been observed. In contrast, when sheep have been inoculated with NSW strains of BTV1, no clinical signs (including fever) have been observed. BTV21 appears to present little risk to sheep as it is difficult to infect sheep with this serotype, and then without any signs of illness.

The distribution of BTV and other economically important arboviruses is determined through NAMP. In NSW BTV transmission is detected in most though not all years. Activity is usually confined to the extreme coastal strip, with infection most frequently encountered on the far North Coast but often south into the Hunter Valley. Although transmission of BTV21 occurred in 2012 on the NW slopes and adjacent plains, this pattern of spread is uncommon and is probably a reflection of the favourable climatic conditions prevailing at the time. On the west of the Great Divide, BTVs have not been detected further south or west and the altitude and cooler conditions of the Northern Tablelands usually prevents or limits vector activity. Along the coastal strip, BTV activity has only been detected south of Sydney on one occasion (1990) when it spread south as far as Bodalla.

The major vector of BTV in Australia is C. brevitarsis, and BTV, Akabane and related Simbu viruses have been found throughout but not beyond its range. In general, Akabane and the related Simbu viruses are transmitted much more efficiently than BTV in Australia. The distribution of these insects provides a sensitive indicator of the presence of C. brevitarsis. Conversely BTV transmission has not been detected in the absence of infection with any of the Simbu viruses. Apart from C. brevitarsis, C.wadai is the only other competent midge found in NSW and occurs intermittently on the far North Coast.

WHAT IS HAPPENING OVERSEAS?

The outbreaks of bluetongue around the Mediterranean Sea (1999-2002) and then the transmission of BTV 8 and several other serotypes of BTV in Western Europe (2006-2009) have been published extensively. BTV-8 transmission has not been detected in Europe recently, probably as a result of the extensive use of vaccine. Several serotypes have been detected recently in Russia for the first time. Their origin remains obscure.

DIAGNOSIS

The BTV blocking ELISA detects antibody to all known serotypes of BTV and has very high sensitivity, detecting antibody in some animals from about 7-10 days after infection. However, the high sensitivity of the ELISA does result in a slight reduction of specificity (about 99.5%), resulting in the detection of some false positives. The incidence of false positives appears to be higher in cattle being intensively managed (eg artificial breeding or AI programmes). Identification of serotype by serology is achieved by VNT but is not routinely undertaken. Cross reactivity between serotypes can complicate interpretation of results.

Bluetongue virus detection has been substantially improved with the availability of real time reverse transcriptase PCR (qRT-PCR). For urgent submissions, samples can be turned around in about 24 hours. At present qRT-PCR is not widely accepted for export purposes but is slowly replacing virus isolation which cost 10 times as much and takes 4-6 weeks to complete. However, interpretation of results and screening of animals/semen for export can be confounded by the extended period in which BTV RNA can be detected - blood samples from cattle may give positive results for more than than 6 months after infection, even though the virus is no longer infectious. In the absence of infection with other serotypes, these animals do eventually give negative results. Research currently being conducted at EMAI is developing qRT-PCR assays that are serotype-specific. Some are in an advanced stage of development and proving to be invaluable for determining which serotype is being transmitted in sentinel cattle. Occasionally there have been suggestions to attempt virus detection in insects for surveillance purposes - and while this is technically feasible, it is an exercise of looking for "a needle in a haystack of global proportions" due to the very small proportion of insects (about 0.5% for C. brevitarsis) that are potentially carrying virus and the logistics of making collections in the brief time when they might be infected.

VACCINES

In Australia, there are no immediate plans for use of vaccines against BTV. AusVetPlan indicates that, in the event of confirmed bluetongue disease in sheep, it is likely that there will be a 'wait and see' period. This is because of the need to confirm the serotype involved, to have a matching vaccine available and to determine the likelihood of a recurrence in the next few years. Experience to date has shown that a high level of transmission in the same region in successive years is unlikely. In the past only modified live vaccines were available and there was an extreme reluctance to use these because of risks of reversion to virulence, capacity to cross the placenta, be excreted in semen and be transmitted by midges. However, largely as a result of the outbreaks in Europe, inactivated vaccines that are safe and highly effective are now commercially available. It is thought that the extensive, compulsory use of these may have contributed to the disappearance of BTV-8 in Europe. Regardless, if there is ever a need to vaccinate in Australia, based on current knowledge and experience, an inactivated vaccine would be used. The only unknown would be the time to availability. If disease was to be caused by a serotype that has not been a major problem elsewhere, there may be a need to develop a new product. In addition to the time delay for production and regulatory approval, supply may still be problematic unless there is strong evidence of the likelihood of sale of large volumes of product.

 


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