Ovine Progressive Pneumonia (OPP)

Introduction: Ovine progressive pneumonia (OPP) is a slowly progressing viral disease of sheep that may affect several different organ systems of the body. Currently, OPP infections in goats are not known to occur outside of laboratory situations. Because the significance of OPP in goats is relatively unknown, the following discussion will focus mainly on sheep.

The disease usually occurs in sheep that are 2-4 years of age. Because the disease does not result in immediate death, affected sheep are often culled. This makes determining the losses due to this disease very difficult. In some flocks the loss may be slight. In others, there may be extensive financial loss from lowered production and death. The difference between severe and minor losses may depend upon the type of management, breed of sheep, strain of virus, and climatic conditions. Some breeds of sheep are probably more susceptible than others to the effects of OPP virus, and some strains of the virus probably cause more disease problems than others. Sheep of the Texel, Border Leicester, and Finnish Landrace breeds appear to develop more frequent and more severe OPP virus-induced disease than do other breeds. A preventive program, which will be discussed later, is currently the most feasible way of lowering the cost of OPP to the industry.

The respiratory form of OPP virus infection in sheep was first described in the United States (Montana) in 1923 by Marsh and was labeled progressive pneumonia. Since then, various names such as Marsh’s, Montana, chronic, and ovine have been used in the name of the disease. A report from South Africa in 1915 described a similar condition called "Graaff-Rinet" disease, named after the region where it was found. This condition and the disease in the United States were compared and considered identical. A similar infection was described in France in 1940 and called "la bouhite," a local name for pulmonary lymphoma; and in Holland in 1943 as "zwoegerziekte," meaning lagging sickness. In Iceland, a pulmonary form of the disease was identified in 1947 as "maedi," meaning dyspnea or difficult breathing; and a paralytic form of the disease was identified in 1957 as "visna," meaning wasting. This resulted in the name maedi-visna that is used to identify the disease in many countries.

Prevalence: Except for Australia and New Zealand, the virus and disease are present in all major sheep producing countries of the world. Infection is common in all ages, breeds, and sexes of sheep throughout North America. The proportion of sheep with serum antibodies to the virus ranges from 1 to 70 percent in different regions of the United States. Antibodies are found most frequently in sheep of the western (30 to 67 percent) and midwestern states (30 percent), with the lowest occurrence in the southern states (Texas 1 percent). Within a geographic region, sheep testing positive for OPP are not uniformly distributed but are concentrated in some flocks. One Idaho flock, composed of several breeds (Rambouillet, Targhee, Columbia, Polypay and Suffolk) constantly had an infection rate of 47 percent for over a decade (1978-1988).

Causative Agent: Ovine progressive pneumonia is caused by a lentivirus (lenti = slow), which is a member of a group of viruses called retroviruses (retro = reverse). The retrovirus family of viruses causes slowly progressing diseases in humans, cattle, cats, horses, and goats (caprine arthritis encephalitis–CAE). The virus that causes CAE in goats is very closely related to the OPP virus.

Lentiviruses have evolved into some very complex relationships with their hosts. Many viruses and bacteria affect only one body system and cause rapid disease with death of the host. In contrast, lentiviruses can induce disease in many body systems and establish lifelong infections that may or may not cause death. Macrophages and lymphocytes normally find a viral invader and then remove it from the body. The characteristics of lentiviruses prevent this normal process from taking place. They avoid removal from the body by infecting and interfering with the immune functions of macrophages and lymphocytes. These characteristics also make the development of vaccines against lentiviruses very difficult for scientists.

Clinical Signs: Sheep that are infected with the virus can exhibit a wide range of clinical signs. During early stages of infection, no signs of disease are apparent. As time passes (two or more years), multiple signs and lesions may develop that can involve one or more organ systems. In individual sheep, signs and lesions may occur alone or in any combination and are often accentuated around lambing time or during other times of stress. However, many infected sheep do not show signs of clinical disease.

Often, the first common sign is a general loss of body condition that can be referred to as "thin ewe syndrome." The weight loss is progressive and occurs despite a normal appetite. The exact cause of this ill-thrift is not understood.

Respiratory problems are also fairly common. Breathing rates are increased at rest, and when moved, the affected sheep ("lungers") tire easily and lag behind the rest of the flock. In the final phases of the disease, affected sheep will lie down much of the time. Coughing occurs when there is secondary pneumonia, but nasal discharge is not often observed.

The respiratory tract problems are caused by changes within the tissues of the lungs. The membrane between air and blood, through which oxygen and carbon dioxide pass, becomes thickened with accumulations of lymphocytes, macrophages, scar tissue, and smooth muscle. These changes progressively reduce the exchange of gases. At death, the lungs are two to three times normal weight, have a rubbery consistency, and are a dull grayish blue to grayish brown color. Nodules, up to one-eighth inch in diameter, can be seen on the surface of the lungs and felt within the lung tissue. These nodules are located around the smaller airways and blood vessels of the lungs and consist of accumulations of lymphocytes.

The OPP virus also can affect the ewe’s udder causing it to enlarge and become firm ("hard-bag"). Milk flow is reduced because of swelling and the accumulation of lymphocytes and macrophages in the tissues surrounding the milk ducts. Some affected ewes do not produce enough milk, especially early in lactation, to nourish a lamb. The udder is not hot and painful and there are no abnormal milk secretions as seen with bacterial mastitis. All hard-bag or firm udder in sheep is not caused by OPP virus infection. Other causes of hard-bag include plant estrogens, hormonal imbalance, and bacterial infections. With these three causes of hard-bag, the firmness is usually reversible and milk secretion increases within a few days after lambing or treatment. Hard-bag caused by the OPP virus, however, is generally irreversible; the only exception to this being a slight increase in milk production a few days after lambing.

The OPP virus may cause lameness and swelling that results in arthritis in one or more joints. Knee (carpus) joints of the front limbs and hock joints of the rear limbs are most commonly affected. This arthritis causes the joint capsule to thicken and become mineralized, and the joint cartilage and bone to deteriorate. The longer the arthritis is present, the more severe the damage to the cartilage and bone of the joint. Microscopically, lymphocytes and macrophages are present in the tissue of the joint.

Inflammation of the central nervous system (brain and spinal cord) is the least frequent form of OPP seen in the United States. The early signs of infection are muscle quivering and loss of balance in the rear quarters. This slowly progresses to paralysis of the hind limbs, with the animal being unable to stand. The brain and spinal cord appear normal when observed with the unaided eye, but microscopic examination reveals excessive numbers of lymphocytes and macrophages around blood vessels, as well as deterioration of the brain. The neurologic signs of OPP are very similar to the signs a goat with the encephalitis form of caprine arthritis (CAE) would have.

Disease Transmission: Ovine progressive pneumonia virus is carried in macrophages in the tissues and fluids of sheep. Secretions from the udder and lungs that carry these cells are believed to be the main sources of transmission for this virus. Other secretions such as saliva and placental fluids may be infectious but this is not proven. Transmission through drinking water contaminated with feces from infected sheep was suspected but has not been substantiated. Urine is not known to be infectious. Transmission through blood, sperm, ova, embryos, or semen has not been adequately studied and cannot be completely ruled out. Likewise, little is known about the stage of infection when a sheep is likely to spread the virus or if all infected sheep spread virus. The virus cannot survive for more than a few days in the environment outside the host animal, especially in hot, dry conditions.

Several studies have shown that transmission occurs between the ewe and her lambs through the colostrum and milk. Ewes in advanced stages of the disease infect their lambs more readily than ewes in early stages of the disease. Also, the longer lambs stay with infected ewes, the greater the risk of transmission of the virus. In a flock that contained OPP virus-infected and non-infected ewes, 37 percent of the lambs born to infected ewes and 20 percent of the lambs born to noninfected ewes became infected with OPP within one year after birth. Transmission of the virus to lambs while they are in the uterus of the ewe is possible but occurs at a very low rate.

Transmission among adult sheep, probably through respiratory secretions, can occur as the result of direct contact primarily in confinement type facilities. Such transmission was documented in a study showing that the introduction of 2 infected ewes into a flock of 22 non-infected ewes resulted in an 80 percent infection rate within 5 years. Other studies show a much lower rate of spread among adult sheep, especially among grazing sheep where transmission is rare.

Diagnosis: Because many sheep carry the virus but do not show signs of sickness, diagnosing animals with OPP cannot be done based on clinical signs alone. In addition, signs of many other diseases mimic those of OPP. For these reasons, an exact (definitive) diagnosis of an OPP infection should be made only after performing additional tests. It should be remembered that methods used to detect either virus or specific antibodies are not 100 percent accurate and may occasionally fail to detect infected sheep (false negative test) or may identify noninfected sheep as infected (false positive test). Therefore, a combination of blood testing and observation of clinical signs are usually necessary in order to detect all cases of OPP.

Detection of virus has traditionally been done by culturing. This is an expensive procedure that requires 12 weeks to complete and only detects about 70 percent of the positive cases. This method, therefore, is unsuitable as a standard diagnostic procedure. Currently, serological tests are the most practical methods for detecting OPP. Two serological tests are commonly used: an agar gel immunodiffusion test (AGID) and an enzyme-linked immunosorbent assay (ELISA) test. Of the two tests, the AGID is the least sensitive and more prone to produce false negative results; however, its specificity and simplicity make it the test of choice for many surveillance and control programs. This is the test most commonly used by diagnostic laboratories in the United States. Because of the higher sensitivity and complexity of the ELISA test, precise conditions are required to produce an accurate result. Consequently, the ELISA test is not as widely available as the AGID. In many laboratories, these tests cannot tell the difference between an OPP and a CAE infection.

New techniques such as polymerase chain reaction (PCR) and antigen capture ELISA (cELISA) are currently being used as methods for identifying OPP viral components in blood, milk, and other tissues of sheep. Some veterinarians recommend that one of these newer tests be combined along with AGID testing when trying to eliminate OPP from a flock.

Care must be used in correctly interpreting serologic results. Actively acquired antibodies (antibodies produced by the infected sheep itself) to the OPP virus are slow to develop and, except for a few cases, are maintained for the life of the animal. In most cases, actively acquired antibodies show that the animal carries the virus. On the other hand, passively acquired antibodies are obtained by a newborn lamb through the colostrum from an infected dam. These antibodies are lost by 6 months of age and do not indicate the lamb has been infected with the virus. Because passively acquired antibodies cannot be distinguished from actively acquired antibodies, serologic tests are uninterpretable during the first 6 months of an animal’s life. With the AGID, some seropositive sheep may become temporarily seronegative following lambing. There is also evidence that a few sheep with severe disease may become seronegative before death. With this information as a background, serological testing is best done in animals older than 6 months and several weeks before or after lambing.

Economic Impact: The overall economic impact of OPP is uncertain. This uncertainty is caused by a lack of scientific investigation comparing the production of OPP-infected flocks with OPP-free flocks under similar management conditions. Variation between different sheep breeds and the way they respond to the virus, and the possible existence of different OPP virus strains also make it difficult to determine economic losses. Direct costs include death, premature culling, increases in the number of orphan and slow-growing lambs because of poor milk production, and possible decreases in fertility and in wool fiber strength. Indirect costs include losses associated with secondary infections, decreased marketing opportunities to OPP-free flock buyers, and a loss of export sales. The amount of financial loss attributed to each of these effects must be measured by individual producers.

Worldwide, the economic impact of OPP varies. In Iceland, maedi-visna is reported to have caused the death of approximately 105,000 sheep and the slaughter of another 650,000 in an attempt to eradicate the disease. The total loss was nearly 30 percent of Iceland’s sheep population. In the Netherlands, maedi-visna was introduced into a flock of Texel sheep and studied over a five-year period. In contrast to the situation in Icelandic sheep, clinical signs of disease and high death losses were rare in the Texel sheep; however, upon inspection, 70 percent of the sheep had maedi-visna lesions in the udder and/or lungs.

North American studies of the effects of OPP on sheep productivity are somewhat conflicting. A study of range sheep consisting of several breeds including Rambouillet, Targhee, Columbia and Polypay showed that lamb and wool production of seropositive range ewes did not differ from seronegative ewes. In comparison, studies in intensively managed farm flocks found that Finnsheep and Cheviot flocks were nonproductive beyond 4 years of age because of OPP disease. These farm flock studies also reported lower weaning weights and reduced numbers of lambs born to OPP-infected ewes. Lower conception rates and lamb birth weights attributed to OPP infection were reported in a Canadian farm flock study. Based on these reports, the degree of economic loss caused by OPP is likely associated with the type of management system, breed of sheep, and intensity of production.

In summary, the economic impact of OPP cannot be fully understood until additional information is obtained. Before control/eradication measures are undertaken, the financial impact of OPP must be assessed at the flock level by the producer and his or her veterinarian.

Treatment: No effective treatment to eliminate OPP infection is currently available; therefore, any treatment will be used to alleviate clinical signs (symptomatic). Most sheep with OPP die of secondary bacterial pneumonia. Antibiotics can be used to treat or prevent secondary infections and may prolong the useful life of a sheep for a few weeks or months. Vaccines for OPP have not been successful. However, the recent success of a vaccine for simian immunodeficiency virus, a lentivirus of monkeys, will encourage continued research efforts. Producers should consult with their veterinarians for specific recommendations.

Eradication Programs: Some producers have successfully eradicated OPP from their flocks by either testing and removing seropositive sheep or by removing newborn lambs from their mothers at birth and artificially rearing them in isolation. Steps recommended in these two procedures are as follows:

Method I - Test and remove:

  1. Take blood samples from all sheep on the farm and test for antibodies to OPP virus. Remove all seropositive animals and their offspring less than one year of age from the flock. Animals removed from the flock can either be sold or isolated in separate facilities. Some experts also recommend testing all goats present on the farm. This is because there is some evidence that goats can be infected with OPP under the right conditions. Many times the serological tests, however, cannot tell the difference between animals infected with OPP and ones that are infected with CAE. Therefore, additional testing and observations are sometimes necessary before a diagnosis of OPP or CAE can be confirmed.
  2. Keep the clean flock isolated from infected animals and isolated from people and equipment in contact with an infected flock.
  3. Add only seronegative sheep to the flock. The additions can be either from other seronegative flocks or from seronegative parents in an infected flock following at least one year of isolation with a negative test reading.
  4. Test annually until there are at least two consecutive negative flock tests to be reasonably sure that the flock is free of the virus. This must be done even when starting with a negative flock. Periodic testing is necessary to ensure that the virus has not been reintroduced into the flock. One should anticipate 3-5 years to eradicate OPP from an infected flock.

Method II - Isolate and artificially rear lambs:

  1. Remove lambs from ewes before nursing and maintain them in isolation from all other sheep and goats. Extreme care must be taken to ensure that newborns do not nurse. The ewe’s teats can be "taped" to prevent nursing. The ewes must not be allowed to lick or nuzzle the lambs.
  2. Proceed with steps 2 through 4 above to ensure virus-free status of the new flock. The virus can be eradicated in one year from the new flock by this procedure, but it is labor-intensive and expensive. An advantage is that valuable genetic stock can be preserved.

Variations of the above methods are helpful in reducing the prevalence of OPP, but eradication requires careful adherence to the recommended methods. Eradication protocols for maedi-visna in Europe advocate testing twice a year. This should hasten eradication but will also add to the expense. In any case, individual, permanent identification and meticulous record keeping are essential for success. An alternative to these eradication methods is to exterminate an existing infected flock and repopulate with sheep that have had at least two negative tests over the previous 2 years. If this method is chosen, producers should clean confinement and concentration areas thoroughly and wait at least 1 month before repopulating with clean sheep. Eradication is expensive and may not be practical in some commercial sheep operations in which a high percentage of the flock is infected. The expense of an eradication program should be justifiable for breeders of sheep who sale to "OPP-free" flock owners or export animals out of the United States.

Conclusion: Ovine progressive pneumonia can occur in any breed of sheep under any management system and environmental condition. However, rates of infection, clinical signs seen, and economic impact vary greatly. General control and eradication methods have proven effective if used in the right situations. With the help of a local veterinarian, a careful analysis of the flock’s historical production, health records, and a producer’s unique conditions should be performed before a decision on how to eradicate OPP can be made.