An outbreak of visna-maedi in a flock of sheep in Southern Brazil.

Visna-maedi is a multisystemic and progressive inflammatory disease caused by a non-oncogenic retrovirus (Visna-maedi virus, VMV). An outbreak of visna-maedi occurred in Southern Brazil in sheep with clinical signs of blindness and stumbling gait. At post-mortem examination, all animals had similar lesions, including heavy non-collapsed lungs and multifocal yellow areas in the cerebral white matter, affecting mainly the periventricular region. These lesions corresponded histologically to lymphocytic interstitial pneumonia and histiocytic periventricular encephalitis surrounding areas of necrosis, in addition to significant demyelination in the brain. Serology was performed in all the sheep from the flock and 14% were seropositive for VMV. The presence of VMV was confirmed through PCR and partial sequencing of the 5'LTR. Sequencing demonstrated that the virus had 89.7 to 90.0% of nucleotide identity with VMV strains reported in the USA. This is the first description of clinical disease related to VMV in Brazil leading to economic losses. This study calls for the need to implement control measures to prevent the spread of small ruminant lentiviruses in Brazil.

Aspects of the epidemiology, research, and control of lentiviral infections of small ruminants and their relevance to Dutch sheep and goat farming.

In 1862, the veterinarian Loman reported the first sheep in The Netherlands with symptoms associated with lentiviral infection, although at the time the symptoms were ascribed to ovine progressive pneumonia. In the following century, similar cases were reported by South African, French, American, and Icelandic researchers. Extensive research into the pathology, aetiology, and epidemiology of this slowly progressive and ultimately fatal disease was initiated in several countries, including the Netherlands. Studies of the causative agents--maedi visna virus (MVV) in sheep and caprine arthritis encephalitis virus (CAEV) in goats, comprising the heterogeneous group of the small ruminant lentiviruses (SRLV)--prompted the development of diagnostic methods and the initiation of disease control programmes in many European countries including the Netherlands, as a pioneer in 1982, and in the U.S.A. and Canada.

Salmonella infection of afferent lymph dendritic cells.

The interactions of Salmonella enterica subspecies I serotype Abortusovis (S. Abortusovis) with ovine afferent lymph dendritic cells (ALDCs) were investigated for their ability to deliver Maedi visna virus (MVV) GAG p25 antigens to ALDCs purified from afferent lymph. Salmonellae were found to enter ALDC populations by a process of cell invasion, as confirmed by electron and confocal microscopy. This led to phenotypical changes in ALDC populations, as defined by CD1b and CD14 expression. No differences in the clearance kinetics of intracellular aroA-negative Salmonella from CD1b+ CD14lo and CD1b+ CD14(-) ALDC populations were noted over 72 h. ALDCs were also shown to present MVV GAG p25 expressed by aroA-negative S. Abortusovis to CD4+ T lymphocytes. Thus, the poor immune responses that Salmonella vaccines elicited in large animal models compared with mice are neither a result of an inability of Salmonella to infect large animal DCs nor an inability of these DCs to present delivered antigens. However, the low efficiency of infection of ALDC compared with macrophages or monocyte-derived DCs may account for the poor immune responses induced in large animal models.

Immune response to maedi-visna virus.

The ovine maedi-visna virus (MVV) was the first lentivirus to be isolated and characterized 1957 in Iceland. MVV leads to a life-long, persistent infection with slow development of lesions in the lung and the central nervous system (CNS). The main target cells of MVV are of the monocyte/macrophage lineage and it does not infect T-lymphocytes or cause immune suppression like human immune deficiency virus (HIV). In spite of a fairly good immune response, including both neutralizing antibodies and cytotoxic T lymphocytes, the virus persists in the host and establishes a life-long infection. There are strong indications that the pathological lesions are immune-mediated and vaccination attempts have not only failed to induce sterile immunity but have occasionally caused increased viremia and more severe disease.

Development of a candidate DNA vaccine against Maedi-Visna virus.

DNA vaccine candidates against Maedi-Visna virus (MVV) infection in ovines were developed as an alternative to conventional vaccines. Candidates were constructed by cloning genes encoding the MVV gag polyprotein and gag proteins p16 and p25 fused to a beta-galactosidase reporter in a plasmid backbone. Transfection of different ovine cells showed a higher protein expression with plasmid lacZp16, which was hence further optimised by (i) removing a putative inhibitory sequence via reduction of the AU-content in the p16 gene or by (ii) introducing a secretory signal (Sc) to promote antigen secretion and increase its presentation to APCs. Unexpectedly, plasmids constructed on the basis of the first strategy by mutagenesis of lacZp16 (lacZp16mut(24)), led to a reduction in the expression of the antigen/reporter fusion in cultured ovine cells. This indicates that the high AU content in MVV does not inhibit protein expression. However, mice primed with lacZp16mut(24) and boosted with MVV protein displayed higher humoral response when compared with control lacZp16. The addition of the Sc signal (Sc-p16) led to lower amounts of intracellular antigen/reporter fusion in transfected ovine cells, thus confirming secretion. These findings correlate with in vivo experiments, which showed that mice primed with Sc-p16 and boosted with MVV exhibited stronger antibody responses when compared with control mice primed with lacZp16 and boosted with MVV. Stronger humoral responses were recorded by immunising mice with (i) Sc-p16 and lacZp16mut(24) plasmids together or with (ii) one plasmid containing both the mutations and the Sc signal.

Establishment of a maedi-visna-free flock after the purchase of infected sheep.

Maedi-visna (MV) infection was detected in a cohort of 68 purchased ewes, one of several groups of sheep introduced to a farm after the previous stock had been culled with suspected foot-and-mouth disease in 2001. Except for short periods totalling six to seven weeks when the sheep co-grazed with 13 ewe lambs and ram lambs, the infected cohort was kept separate from other sheep on the farm over a total of 21 months. During this period two crops of lambs were reared from the infected ewes. All the lambs were fattened and killed, and all ewes were culled after the second crop of lambs had been weaned. Subsequent serological testing of the remaining sheep on the farm confirmed the elimination of MV infection from the flock, leading to its acceptance in the Maedi Visna Accreditation Scheme of the Scottish Agricultural College's Sheep and Goat Health Schemes.

Failure of experimental vaccines to protect against infection with ovine progressive pneumonia (maedi-visna) virus.

Cell culture medium was harvested from cells infected with ovine progressive pneumonia (OPP) virus and used to prepare killed virus vaccines. Virus was inactivated by either heat, formalin, or ethyleneimine and used either without adjuvant, with Freund incomplete adjuvant, or with aluminum hydroxide adjuvant to vaccinate sheep. The sheep produced precipitating antibody against the virus but were not protected against infection when challenged with live OPP virus.

Maedi-visna control in sheep. I. Artificial rearing of colostrum-deprived lambs.

A field trial to study the practicability and efficacy of maedi-visna control in sheep by artificial rearing of lambs was carried out during the lambing season of 1979. Lambs were immediately separated from the dams at birth, deprived of ovine colostrum, and reared isolated from the parent flock. Bovine colostrum was given instead of maternal colostrum. Eleven farms participated in the experiment. All flocks were severely infected with maedi-visna virus: 63-100% of the ewes were seropositive as demonstrated by ELISA. Artificially reared lambs were serologically tested and positives culled at the age of 6, 12, 18, 24, 30 and 36 months. Only very few positives were found: 1/389, 1/376, 0/337, 1/223, 1/192 and 0/144, respectively. The first two sero-positive lambs occurred in one flock, and it could be ascertained that both had mistakenly been given ovine colostrum probably containing maedi-visna virus. No explanation, other than sub-optimal hygiene and isolation, could be found for the two sero-positive sheep that turned up in another flock at 24 and 30 months of age although, transplacental infection cannot be entirely excluded. It is concluded that artificial rearing of ovine colostrum-deprived lambs is an effective and practicable method for the control of maedi-visna in sheep. The method appears particularly useful when valuable genetic material has to be salvaged.

Maedi-visna control in sheep II. Half-yearly serological testing with culling of positive ewes and progeny.

In 1979 a field trial was started to study the feasibility of maedi-visna control in sheep by half-yearly serological testing (by ELISA) with culling of sero-positive ewes and their progeny. In 13 commercial flocks, with a mean initial incidence of serological reactors of 17%, the sero-positive ewes and all their progeny, those of preceding years included, were culled after each half-yearly test. The percentage of sero-positive sheep decreased gradually and at the end of the second year, at the 5th test, all flocks were sero-negative. Also the 6th and 7th test did not yield sero-positive sheep. At the 8th test, however, 3 sero-positive ewes were detected in one of the flocks. A definite conclusion as to the source of infection could not be drawn. The following flock test was negative. In 2 other commercial flocks, which had a mean initial incidence of sero-positive sheep of 53%, those sero-positive and only their suckling lambs were culled. Here too, a gradual decrease in the incidence of sero-positive sheep was observed at the 2nd and 3rd test, but at the 4th test a sharp increase occurred. The programme was continued and a decrease followed until 0% was reached at the 7th test (end of third year). Age analysis of the sero-positive sheep which caused this peak revealed that the majority had been born before the start of the trial. This suggests that a 'second wave' of sero-positive sheep may be prevented and a quicker result obtained if progeny of preceding years are culled as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Maedi-Visna virus infection in sheep. History and present knowledge.

Briefly the history of maedi-visna and the major clinical symptoms are described. Examples are presented to demonstrate that the genetic composition of a breed determines whether or not sheep become sick after an infection with maedi-visna virus (mvv) or develop solely specific antibodies. The major pathway of transmission is not colostrum and milk, but a cell containing increased nasal discharge in cases of respiratory distress. The role of the environment and prophylactic measures against parasites is stressed, because even sheep of highly susceptible breeds can survive an infection under optimal conditions. The virus and subsequently the disease simply die out. The cooperation between clinicians and laboratories is necessary.

A simple method for the demonstration of factors in bovine colostrum capable of causing anaemia in lambs reared free from maedi on bovine colostrum.

Previous studies demonstrated that the anaemia encountered in lambs reared on bovine colostrum and a milk substitute was associated with the presence of immune complexes on lamb erythrocytes. In the present study the usefulness of a panel of 20 sheep sera for the detection of "anti-sheep" factors in bovine colostrum by double immunodiffusion in agarose was investigated. Utilising this method, 353 batches of bovine colostrum have been examined, 132 of which were declared safe for use in the rearing of lambs. When fed to lambs, only 2 samples (1.5%) caused anaemia as compared with up to 20% before this test was introduced. Experiments designed to determine whether the bovine colostra, declared anaemia-prone, would indeed cause anaemia when fed to lambs, showed our method to fully discriminate between safe and unsafe colostra for the rearing of lambs. In a follow-up collaborative study, set up to cover most of the Netherlands, the general validity of the test system described was demonstrated, using 114 batches of safe colostrum to feed 723 lambs. Further experiments are needed to determine the exact nature of the factor(s) involved in this phenomenon.

Preventing the spread of maedi-visna in sheep through a voluntary control programme in Finland.

The sheep disease maedi-visna (MV) was introduced into Finland in 1981 and had spread to eight flocks in the southwestern part of the country when first detected in a survey in 1994. Six more seropositive flocks were subsequently traced, bringing the total to 14. MV has a notifiable disease status in Finland that provides for official restrictive measures to which all infected herds are subject. These measures are withdrawn once the seropositive animals and their progeny are culled and the flock has showed negative signs in the test done twice, or after total culling. A voluntary control programme was initiated in January 1995 to extend official control efforts. The programme furnishes a guideline for culling, restrictions on contacts, and a timetable for testing the flock to attain MV-free status. Seven flocks of the 14 were slaughtered either immediately or after a period under restrictive measures. One flock finished sheep production after four years under restrictive measures. Selective culling and repeated testing was attempted with the other six flocks, three of which attained MV-free status. One flock finished sheep production after two years in the control programme, the other two dropped out of the programme when the restrictive measures were withdrawn. It was concluded that the control programme was salient in eradicating MV from Finland and that serological monitoring of the situation must be continuous.

Transmission and control implications of seroconversion to Maedi-Visna virus in Basque dairy-sheep flocks.

A retrospective analysis of seroconversion to Maedi-Visna virus (MVV) was carried out for 10 infected semi-intensively reared dairy-sheep flocks that were tested annually between 1994 and 1999. Four of the flocks raised replacement lambs artificially with bovine colostrum and milk replacement to avoid lactogenic MVV infection but did not prevent aerosol contact between replacements and other sheep in the flock. Flock culling percentages ranged between 14 and 25% and in eight flocks the number of sheep that seroconverted was similar to or lower than the number of sheep culled--suggesting that incidence could be reduced by culling seropositive sheep without increasing average culling percentages. Random-effects logistic regression indicated that seroconversion was associated positively with increasing contact with infected sheep and with lifetime MV-serological status of the dam (used as a proxy measure of genetic susceptibility), but not with mode of rearing pre-weaning (artificially or with a seropositive or seronegative dam). Our results indicate that when conditions allow efficient horizontal transmission, there is no evidence that lactogenic infection increases the risk of MV infection and that there is an important inheritable component of disease resistance or susceptibility.

Evaluation of two management procedures for the control of maedi-visna.

Two control programs were evaluated for their efficiency in eradicating the maedi-visna (M-V) virus from a single sheep flock. In both programs, the agar gel immunodiffusion test was used for the detection of M-V infected animals at regular intervals. In program 1, the test and remove program, ewes that were serologically positive for M-V were immediately removed along with their offspring. The prevalence of infected sheep decreased gradually and a seronegative flock was obtained after 30 months of monitoring. Program 2 entailed the removal of replacement ewe lambs at birth prior to the ingestion of colostrum. Maedi-visna antibodies have not been detected in this flock. These results show that under conditions similar to the industry norms, M-V can be expelled. Although the approach of program 1 is more practical for sheep producers, program 2 is more effective because of the earlier development of a M-V seronegative flock. Because of the nature of the humoral response, a longer time period than four years is required to ensure that M-V has been completely eradicated from each flock.

Eradication of ovine progressive pneumonia from sheep flocks.

Two management methods for controlling ovine progressive pneumonia in sheep were evaluated. By a test and cull method, wherein seropositive sheep were culled from the flock, the causative virus was eradicated from a closed flock and controlled in an open flock. By an isolate-and-test method, wherein lambs were removed from infected ewes before nursing and reared in isolation, the virus was eradicated in 1 of 2 attempts to establish virus-free flocks. It was concluded that either method should be effective in controlling ovine progressive pneumonia. Results indicated that annual serologic monitoring of a virus-free flock would be necessary to ensure that the virus-free status is maintained.

Maedi-visna control in sheep. III: Results and evaluation of a voluntary control program in The Netherlands over a period of four years.

The results of the first four years of the Dutch national voluntary maedi-visna control program, which was launched on January 1, 1982, are presented. At the end of the observation period, 1711 breeding flocks representing 70% of the registered breeding flocks participated. The program is based on accreditation of flocks that have passed two successive serological tests with an interval of six months between and post-accreditation tests every 12 months. The flocks have to conform to a set of specific regulations. Sheep sold from such flocks receive a certificate stating that their origin was accredited. A total of 1212 flocks gained accreditation. Of these flocks, 29.5% were free from infection from the beginning, 35.6% were created by total replacement of the original stock, 19.6% employed repeated testing and culling of positives, and 15.3% were created by artificial rearing of colostrum-deprived lambs. A total of 22 flocks lost accreditation due to detection of 36 seropositives. These positives and their progeny were culled, and all flocks regained accreditation after passing the two negative flock tests required. In a total of seven flocks, an unusual course of events during the pre-accreditation stage was observed; this was mainly attributed to late seroconversions and uncommon degrees of horizontal transmission. The results indicate that this certification yields a substantial guarantee of freedom from maedi-visna virus and they indirectly show that the basic design of the program has been adequate.

Maedi/visna: a review.

A brief history of the occurrence of maedi/visna or maedi/visna related diseases is given. The clinical features and diagnosis are described. Recent experimental work performed in an attempt to resolve the pathogenetic features of slowness and persistence of infection, characteristic of maedi/visna, is covered. A description of the epidemiology is given followed by possible methods of control.

[Pilot project for eradicating maedi-visna in Walliser blacknose sheep]. / Pilotprojekt zur Sanierung der Maedi-Visna bei Walliser Schwarznasenschafen.

Maedi-Visna is a lentiviral disease of sheep with a worldwide distribution. The transmission of the virus occurs primarily via colostrum and milk from the infected ewe to its newborn lamb but also horizontally between sheep. The most obvious clinical symptoms are progressive dyspnea and emaciation. In this prospective study an eradication based on serological testing and removing of seropositive animals was performed in 24 flocks of sheep of the breed "Walliser Schwarznasenschafe" leading to a reduction of the seroprevalence from 36% to 1% within two years. The control group consisted of 21 flocks of sheep. Lambs of seropositive ewes had a 7.6 times higher risk to seroconvert within their first two years of life compared to those of seronegative ewes. The dynamics of the spread of the infection were studied in birth cohort groups. Cohort animals of seropositive ewes showed an obvious trend to seroconvert slowly. Seropositive ewes had a significantly lower reproduction rate and their lambs suffered from significantly higher death and lower growth rates, probably due to a reduced milk production, resulting in economic losses.

[Maedi and maedi control (author's transl)]. / Zwoegerziekte en zwoegerziektebestrijding.

Maedi/visna is a chronic progressive interstitial pneumonia of sheep caused by a persistent infection with a retrovirus. Approximately thirty per cent of the sheep population in the Netherlands carries antibodies to maedi virus. An experimental eradication scheme based upon serological testing with ELISA and culling of reactors every six months was started, recently. Initially, 353 (25.4 per cent) reactors were identified among 1391 sheep in sixteen flocks, whereas the second test, six months later, showed 130/1111(11.7 per cent) reactors. On 11 other farms with high infection level 382 lambs were separated from their dams immediately after birth, ovine colostrum deprived and artificially reared. The lambs were serotested at 6 months of age and 2/382 (0.5 per cent) were found positive, while naturally reared lambs on the same farms scored 39 per cent positive.

[Comparison of a number of parameters in the blood of lambs reared in normal conditions with those in the blood of lambs reared free from maedi on bovine colostrum (author's transl)]. / Een vergelijking van een aantal parameters in het bloed van normaal opgefokte lammeren en van lammeren die zwoegervrij, met runder-colostrum zijn opgefokt.

The results of examination of the blood in a group of lambs reared free from maedi on bovine colostrum were compared with those in a group of controls reared in normal conditions. Examination of the blood included determination of the concentration of haemoglobin, the haematocrit, white cell counts, platelet counts, the total lipid level, the concentration of protein in the serum and the protein pattern of the serum. The group of experimental animals and that of the controls were found to show only minor differences as regards these constituents. The studies showed that lambs are capable of adequately absorbing the immunoglobulins of bovine colostrum.