Review of warblecide epidemiology
MAFF 1989 warble surveillance report
Warble incidence in UK by serology
Listserve opinions

Review of warblecide epidemiology

From: Torsten Brinch
Mark Purdey's account

It was the peculiar geographical distribution of BSE in the UK which made Mark Purdey put forward the hypothesis, that warblecide could be involved in the causation of BSE. Obviously a comparison of the epidemiological features in time and space of BSE with the timing and geographical distribution of warblecide treatments would be the most promising possibility to disprove Mark Purdey's hypothesis.

In one of the initial epidemiological studies on BSE (Vet Rec 1988 123, 663-644), Wilesmith et al. specifically state the range of pharmaceutica examined, and excluded as common factors. "These included the use of vaccines, hormones, organo- phosphorous fly sprays, synthetic pyrethroid sprays and ear tags and anthelminthics". Also on-farm use of herbicides and pesticides were examined and excluded. Warblecide pour-on treatments are not mentioned in the 1988 Wilesmith et al. study.

The necessity for excluding these factors stems from the epidemiological features of the disease which are compatible with a causative agent spread by human intervention, like foodstuffs, medical treatments or agrochemicals. At the time of the initial study the association between the time of onset of clinical symptoms and calendar month or stage of pregnancy could not be perceived. An association would be expected if medical treatments or agrochemicals were involved. The apparent lack of any association contributed to the selection of the working hypothesis that the causative agent is spread with feedstuffs. This hypothesis has guided research ever since.

The seasonal variation became apparent and was noted by Wilesmith (Vet.Rec. 1992, 130 90-94) "the apparent seasonal variations ... are being studied in relation to the potential seasonality of exposure, given the seasonality of calving and the feeding of calves with concentrate rations." This seems to suggest that seasonal exposure (to calves) are responsible.

It has been suggested that the seasonality of farming practices, housing, calving and opportunities for inspecting could explain the seasonality. This may well be the true cause. The seasonality is clearly present, the ratio between numbers of clinical onset at maximum (Dec-Jan) and minimum (May-Jun) is appr. 1.3.

The strongest disproof of this hypothesis would be inconsistency between which cows (or unborn calves) were exposed to warblecide, and which cows contracted the disease. Warblecide treatments are given in the autumn (August AFAIK) when the adult warble fly has stopped propagating eggs. The treatment cannot be delayed much, because the larvae in November-December reaches the spinal chord, and treatment at this stage can lead to serious fatal adverse reaction to larvae dying in the vertebral canal.

Treatments with warblecide thus coincide with or slightly predecess the peak calving season (August-October) in the UK. Although treatment of pregnant and dairy cows with OP's are generally not recommendable, they do not seem to have been excempted from treatment in the UK warble eradication campaign 1978-81 and in the following years.

Voluntary treatments commenced, presumably to the largest extent in regions which were still warble-infested in the late eigthies. The MAFF 1989 surveillance report recognizes that voluntary treatments were used in prophylaxis, and have probably been a key factor in the virtual eradication of warbles in most areas of UK by 1990. Experience from eradication campaigns in Ireland shows that infestation with warbles may spread quickly a few years after a successful campaign unless prophylactic treatments are continued. The OP treatments that were employed in the late eighties were predominantly phosmet treatments -- other OP's (mainly fenthion) were used during the compulsory eradication campaign 1978-1981.

The MAFF 1989 surveillance report mentions the widespread use of ivermectin anthelminthics as a contributing factor. Ivermectin is also warblecidal. Serious adverse drug experiences with ivermectin are not uncommon, and the drug has teratogenic properties -- Ivermectin should be looked at very carefully in order to exclude it as a contributing factor to BSE, if this has not been done already.

The large majority of BSE-cases were born in the 1986-1988 calving seasons. *Maybe* the cases in these cohorts were not treated with warblecidal products, maybe not. If this can be demonstrated, warblecides can be excluded as causative agent for BSE. There does not seem to be any published studies. If warblecide treatments are involved at all exposure in utero (last trimester) or in early calfhood is the most likely timing scenario. If this is not recognized by the (hypothetical) study or trial, they are of limited value. Studies must focus on *specific treatments* in *specific circumstances* with a *specific OP*.

Links to resources on veterinary drugs, veterinary parasite management and entomology on the larval stage 'cattle grubs' of warble flies (Hypoderma).

Excerpts from MAFF 1989 warble surveillance report:

"A comparison of the 1989 results with those of the more limited 1988 survey shows that, despite the greater number of sera tested fewer seropositive herds were found in the northern and eastern counties, the eastern half of the country being now virtually free of serological evidence of the disease. Contributory factors to this result probably include continued voluntary treatments, and the use of ivermectin on a wide scale for helminth control"

"On the other hand, the counties in mid and west Wales reveal an apparent extension of the area affected, with one seropositive farm as far west as Carmarthen.... Without additional measures to ensure full coverage of prophylactic treatment, these infestations will probably persist and may spread by stock sold-on to farms in other areas."

"The results from the west country show little change from the previous season. The lack of seropositive animals from west Cornwall could be due to the fact that many herds were treated after the 1988 survey"

"The low levels of the disease indicated by this survey should not be a cause for complacency .... It is to easy to conclude that prophylactic treatment is no longer necessary"

"This survey demonstrates that one obstacle to the eradication of warble fly is the assumption that a failure to detect signs of warbles on cursory inspection is an adequate basis for the belief that autumn dressing is no longer necessary."

(Sinclair et al. Vet.Rec.(1990) 126, 327-329)

27 May 1996 Listserve item from:: Torsten Brinch

The MAFF serological survey method was published in 1983 and it was used in the UK at least as late as 1992. An immunological test, it measures accurately whether a cow has ever been infected by the warbles fly. There are 12,000,000 cattle; an average of 25 per herd.

Warbles in UK by Serology
YearReported Per millionTotal cases
1985 419 n/a n/a
1986 34 n/a n/a
1987 8 n/a n/a
1988 4 390 4700
1989 2 250 3100

Source: Sci.Agriculture 9th May 1996.
Chief Vet Officer's Report 1981 (UK) stated:

A large scale serological survey showed in 1978 that 20% of cattle in the UK had had an infection of warble fly. Warble fly compulsory treatment zones were for farms within a 3km radius of an infected farm. So a zone in Oxfordshire would not be some huge area, but a very small local zone of 3km radius. The number of farms that were placed under order in 1982 was 1589.

The number of British cattle visually reported infected [less sensitive than serological detection] since 1985, and two infected importations (total cattle population of about 12,000,000):

Year UK infectedRate/million ImportedCases
1985 419 35 1993 207
1986 34 2.8 1992 43
1987 8 0.7
1988 4 0.3
1989 2 0.2
90-95 1 0.1

Listserve item 27 May 96:

"Recent survey from Germany (where it is apparently the law that infected cattle should be treated) in Rheinland gave 30% of herds infected with warbles. In France any herd with more than 5% warbles are by law obliged to treat the whole herd. Apparently this is done by Department and 'some police this more than others'.

So it is quite clear that treatment for warbles is not confined to the UK in the three years of the eradication scheme. There were, and are, very significant usages of these products in the continental EC which continue to this day. At least some countries have laws requiring treatment, and I would expect the majority of welfare conscious farmers would treat anyway. The minority who don't spreading the problem to those that do.

One should also note that only one product can be used on milking cows with an acceptable milk withdrawal period (I believe Phorate), which is indeed an OP. Ivermectin is rather persistent, so cannot practicably be used on dairy cows.

Generally Phosmet wasn't used except in areas with lots of mites, typically upland areas. About 1/3 of the UK used Tiguvon for example. Spraying for warble fly eradicated the disease. Our operation has not treated any cattle with insecticides since 1981; this would be typical of the majority of farmers."

Listserve item, 28 May 96:

The warblefly larva makes its way near/into the spinal column, so a good way (200,000x better than oral route) to innoculate CSF/CNS with prions. Are there already studies/data which show no obvious relation between warbles being in an animal and it having BSE?

Listserve item, 27 May 96:

The warble fly is similar to the screw fly [or heel fly] of America. It lays its eggs on the legs of cattle. When they hatch they burrow under the skin and deep into the body and munch their way (over a year) through the cows body until they are just under the skin over the spine. Eventually they chew their way out and drop to the ground, a legless grub about (from memory) 25+mm x 10mm. They then pupate and hatch on the ground.

There was a suggestion that BSE was directly caused by the once-annual treatment against this pest with the organophosphate, Phosmet, when the UK sought to eradicate it. The case against this proposal is pretty solid.

Organophosphates are used on cattle the continent, America, Australia and many other places without BSE appearing. Indeed in hot climates they may be used several times a year. The amount of pour-on OP's used on the continent was many, many, times greater than the UK 82-90 since the UK rarely identified more than the low hundreds per annum in these years (except for the odd batch of imported cattle). Why has BSE not appeared in these other places? Politically it would be nice to blame it on OP's, a simple ban on OP's should stop the problem in it's tracks.

Pesticide linked to Britain's Mad Cow epidemic

ENN Daily News -- April 8, 1996

Excessive use of an organo-phosphate pesticide more than 10 years ago could have caused Britain's epidemic of Mad Cow disease, a farmer-researcher told the Edinburgh International Science Festival Saturday. Organo-phosphate chemicals are widely used as pesticides in agriculture, horticulture, fish farming, forestry and veterinary medicine and in the home for medicated shampoos, fly-sprays and flame retardant clothing or bedding, Mark Purdey said.

Purdey said farmers were forced to use phosnet -- a blend of organo-phosphates and base of the drug thalidomide -- in the 1980s to combat warble fly infestation. Massaging it into a beast's rump to ensure it penetrated hide, flesh and muscle and reached deep-burrowing larvae meant OP toxins affected the animal's nervous system. Purdey successfully defended himself against an Agriculture Ministry prosecution for refusing to use phosnet. He then began to study organic chemistry to back his practical experience with scientific knowledge.

In the process he lost his farm, was shot at, blockaded in his home to prevent him giving a lecture, and saw a new farmhouse go up in flames the day he was due to move in. Purdey says it was significant that Switzerland, the only other European country to insist on the use of phosnet is the only other European country with large-scale BSE (bovine spongiform encephalopathy) outbreaks. OPs readily cross body barriers and bind with crucial nerve enzymes, disrupting pathways of the central, peripheral and autonomic nervous systems, Purdey said.