My thoughts on reading the EFSA document on the Schmallenberg virus.by Ruth Watkins 8/2/12
There are so many unkowns about the Schmallenberg virus at present that the comparison with BTV8 in Northern Europe (that was conquered by vaccination) by EFSA seems a good one, and the known one to compare with.
I don't think they do this well and there is insufficient comparison with Akabane virus.
BTV8 was in a way more straightforward than this orthobunyavirus- almost without exception the only animals to be infected and symptomatic with BTV8 were the ruminant herbivores (excepting some deer) and the vector was the Culicoides midge mainly the species de wulfi. The virus was not transmitted vertically in the midge and is thought either to have survived in long lived populations of females in winter barns or through biting in the Spring of persistently viraemic calves, that were for the most part well and not identified, born without any disease from infection in utero. It is also probable the viraemia in infected post-natal ruminant herbivores, (other than the young infected in utero see above which was persistent), was more long lived that that with Schmallenberg virus, by a factor of at least 2 or 3 times.
Vaccinating the ruminant herbivores against BTV8 using a killed vaccine was sufficient to interrupt the transmission so that the virus was eliminated from the area where it had become endemic within 2 years.
How has Schmallenberg virus emerged so suddenly and in one year affected a much larger area than BTV8 did initially in 2006?
I am not sure how likely this is due to infected animals arriving. This experiment is being done in the UK - the area affected so far is that in the wind-blown midge area and not as yet in any of the areas where animals from Northern Europe have been imported all summer long all over the UK. In endemic areas of Akabane virus infection the epidemics occur when weather conditions are favourable for the vectors to breed and move or be moved to peripheral areas where the hosts are susceptible. I am not sure there are any restrictions on moving animals in case they might have Akabane virus infection.
I suspect it is the movement of infected vectors on the wind from the Middle East or from North Africa that has brought this virus.
The modelling mathematics of r0 does not apply in the case of Schmallenberg virus but they do not explain why. The assessment of the differences after wasting a lot of mathematical wool pulling on r0 is much too superficial. They as much as say the 'simple equation' they put forward would not explain this epidemic.
There are likely to be a number of vectors involved in Schmallenberg virus transmission - mosquito species (plural) and midge species (plural).
The relationship of the virus with each vector is likely to be different.
For each there is the question of susceptibility of the females to infection via a blood meal. This starts with infection of the midgut and then spreads throughout the body in the heamocoel, insect blood, infecting various organs including the salivary glands so it is transmitted in biting, and the sexual organs so that it can infect the egg for vertical spread. If the infected egg hatches into a male the gonads can be infected so that venereal transmission can occur to an uninfected fertilised female insect from the infected male.
Orthobunyaviruses and Akabane in particular are known to infect mosquitoes by vertical infection- the infected female laying infected eggs that hatch into infected new adults. I have not found any papers showing this is the case for Akabane virus in the midge species that it is known to infect in either Japan, Israel or Australia. However I am not sure if these experiments have been done on midges.
It is clear that in tissue culture or in-vivo Akabane virus does not have any cytopathic effect on insect cells and gives a persistent infection, in contrast to that on mammalian cells where it is cytopathic.
There may be one or more vectors important for persistence of the virus in unfavourable seasons for example, and another or others that are most important in an epidemic when the weather is favourable to the vector(s) so that infection is quickly amplified.
Another consideration in contrast to bluetongue virus, is that if vertical infection (trans-ovarial transmission) takes place a midge species that bites only once and not multiple times could also take part in the transmission cycle as its female progeny will be infected before they have taken their single blood meal.
For each orthobunyavirus strain and type of insect, and perhaps temperature for instance, there will be a competence of infection. The competence of infection is a combination of oral infectivity, trans ovarial transmission and number of progeny infectious. It is interesting that this is almost a 100% for one mosquito species in the case of Rift Valley fever, Culex pipiens, whereas this is only some 30 % or less in other species of mosquito (there is an interesting article on up to date work on Rift Valley Fever to be found on Google Scholar).
Orthobunyaviruses are variable and several strains can co-circulate as in Japan, so that immunity to one does not give complete immunity to another (the antigens responsible for neutralising antibody, the protective antibody, are found on the Middle segment of the tripartite genome). Reassortment, the mixing of the 3 separate single stranded RNA genome fragments, Small, Medium and Large, from 2 different orthobunyavirus in the same group occurs in insects for example. This is when a vertically infected insect is exposed to a different genetic strain by becoming infected in its blood meal. I am not sure if Akabane is intrinsically more variable than BTV8: Orthobunyaviruses are single stranded and Orbiviruses (inc Bluetongue) are double stranded.
In Japan a trivalent killed vaccine has been prepared using 3 viruses, Aino, Akabane and Chuzan and reported in 2011 (Aino and Akabane are orthobunyaviruses and Chuzan an orbivirus). It is anticipated that this should prevent disease of the ruminant foetus of cattle sheep and goats if given (2 doses) prior to pregnancy.
I should also point out that Akabane virus infects more types of animals than those in which the foetus is damaged (or there may be meningo-encephalitis as well in post natal cattle). For instance horses, donkeys, pigs and dogs. I don't know how complete this list is and whether small rodents for instance may also be infected. Also I am not sure if these, whilst not exhibiting disease, could play a role in amplifying infection by having a viraemia high enough to infect a biting midge or mosquito. In the case of pigs, infection by the oral route has been demostrated experimentally but not horizontal transmission from the virus shed from the oropharyngeal tract. Where Akabane is endemic then there is serological proof of infection of many pigs by the time they are ready for slaughter, but this of course in the field could be due to mosquito or midge bites. Horizontal transmission is being flagged up too heavily; it is remote and with no proven precedent.
It might look from this that Schmallenberg virus is definitely here to stay and spread through out Northern Europe. One cannot say without the detailed entomology of virus infection, which is mentioned but not greatly enough emphasised in the EFSA document. I think this needs to be well funded by the EU. It seems to me to be greatly lacking.
Dr Ruth Watkins formerly held the very senior post of Head of Diagnostic Virology at St Mary's Hospital where she was an Honorary Consultant and Senior Lecturer in the Department of Virology at St Mary's Hospital Medical School, Imperial College School of Medicine, London. She is currently a sheep farmer in Wales. With her invaluable expertise in virology, coupled with her knowledge of farming, it is important that her views are listened to. (Taken from a comment from www.land-care.org.uk )