Small ruminant lentiviruses: economic and productive losses, consequences of the disease Lentiviroses de pequenos ruminantes: perdas produtivas e econômicas, consequências da doença

Small arthritis encephalitis virus, and Maedi-Visna virus cause diseases that result in significant productive losses, mostly in dairy animals. These viruses belong to the Retroviridae family, Lentivirus genus, and constitute a heterogeneous group, which may generate implications for the diagnosis and control of small ruminant lentiviruses. Losses caused by them are associated with reproductive failure, short productive life, and decreased milk production by the infected animals. In addition, these viruses may reduce milk quality, affecting the production of dairy products such as cheese. Small ruminant lentiviruses lead to indirect losses, decreasing herd value and forcing the development of epidemiological trade barriers for animal germplasm. Control of small ruminant lentiviruses is important to promote optimal milk production and to reduce costs with medicine and technical assistance. This control may vary in caprine and ovine populations of each country, according to seroprevalence, variety of breeds, and peculiarities of the practiced management.

ABSTRACT: Small ruminant lentiviruses, caprine arthritis encephalitis virus, and Maedi-Visna virus cause diseases that result in significant productive losses, mostly in dairy animals. These viruses belong to the Retroviridae family, Lentivirus genus, and constitute a heterogeneous group, which may generate implications for the diagnosis and control of small ruminant lentiviruses. Losses caused by them are associated with reproductive failure, short productive life, and decreased milk production by the infected animals. In addition, these viruses may reduce milk quality, affecting the production of dairy products such as cheese. Small ruminant lentiviruses lead to indirect losses, decreasing herd value and forcing the development of epidemiological trade barriers for animal germplasm. Control of small ruminant lentiviruses is important to promote optimal milk production and to reduce costs with medicine and technical assistance. This control may vary in caprine and ovine populations of each country, according to seroprevalence, variety of breeds, and peculiarities of the practiced management.
Target cells for small ruminant lentiviruses are monocytes/ macrophages, which are defense cells found in the organisms of animals (NARAYAN et al., 1982). These viruses may be found in a high concentration in infected tissues and fluids, even in tissues that are not usually a preference for viral replication. The presence of SRLV has been identified in blood, colostrum and milk (LARA et al., 2003), cerebrospinal fluid (SIDER et al., 2010), uterine fluid and semen (ANDRIOLI, 2001;ANDRIOLI et al., 2006). In addition, these pathogens have been identified directly or indirectly in third eyelid tissue (CAPUCCHIO et al., 2003), goat epithelial cells of oviduct (LAMARA et al., 2002), uterine tissue (FIENI et al., 2003), mammary gland (LERONDELLE et al., 1999), and lung (BARROSO, 2013). These viruses have been identified in the central nervous system (SANNA et al., 1999), stromal cells of bone marrow in fibrocytes, endothelial cells and adipocytes (GROSSI et al., 2005). Viral transmission occurs directly or indirectly by secretions rich in cells of the monocyte/macrophage system, especially macrophages. The main form of transmission is digestive, through the ingestion of colostrum and/or milk of infected goats and sheep. The aerosolized transmission is very important for MV, considering that the main form of clinical disease is respiratory (DAWSON, 1987;MOOJEN, 2001). In addition, direct transmission may occur through the reflux of contaminated milk in deregulated milking machine, contaminated fomites, such as towels, needles, tattoo and dehorning equipment (ROWE; EAST, 1997) or artificial insemination . Intrauterine transmission has not been discarded yet (ALVES, 2015). Interspecies transmission of SRLV is mainly through the contact of infected sheep and goats and by the ingestion of contaminated colostrum or milk of infected goat nannies (SOUZA et al., 2015b). In 2015, SOUZA et al. (2015a demonstrated the virus in saliva, which may play an important role in the epidemiology of the disease if it is infectious. SRLV may be detected directly or indirectly. Among the detection methods, viral isolation in cellular culture, electronic microscopy, in situ hybridization and polymerase chain reaction tests are direct forms. Indirect methods are performed with the detection of antibodies in serological tests. The most frequently used serological techniques for diagnosing SRLV infections are agarose gel immunodiffusion (AGID), indirect immunofluorescence assay (IFA), immunohistochemistry, and immunoassays: Enzyme-linked Immunosorbent Assay (ELISA), Dot-Blot, and Western Blot (WB). The AGID is a practical test with low cost and one of the indicated methods by the World Organization for Animal Health (OIE). It is used in screening, considering the acceptable sensitivity and excellent specificity it presents. However, it fails to detect animals with low titers of antibodies, allowing the occurrence of false-negative individuals within the flock. As a result, the virus is maintained and transmitted from positive animals that were not identified to healthy individuals (ANDRÉS et al., 2005;RODRIGUES et al., 2014;PINHEIRO et al., 2012). PINHEIRO et al. (2012) evaluated the sensitivity of AGID, ELISA and WB with a serial dilution of SRLV-positive serum and verified that AGID presented detectable precipitation line up until 1:8 dilution. Positive results were identified with ELISA up to 1:64 and with WB until 1:1024. These data demonstrate that WB may detect antibodies in a dilution 128 times higher than AGID and 16 times higher than ELISA.
SRLV infection usually presents a long period of incubation with frequent occurrence of asymptomatic infections on top of diagnostic limitations. These happen due to genetic and antigenic relations of SRLV, which allow the occurrence of false-negative animals in flocks. These characteristics are limiting factors for controlling SRLV diseases, which lead to significant economic losses, mainly in dairy production. In addition, SRLV may migrate to several different tissues and fluids, hindering the detection and favoring transmission (PISONI et al., 2007), including interspecies (SOUZA et al., 2015b).

ECONOMIC AND PRODUCTIVE LOSSES
These diseases cause direct losses, such as decrease in the productive life length and milk production; shorter duration of lactating period; predisposal for bacterial infections especially in the mammary gland; and reduction in fat and protein levels of milk produced by the infected goats, which affect dairy products such as cheese production (SMITH; CUTLIP, 1988;GREGORY et al., 2009;BRITO, 2009;MARTÍNEZ-NAVALÓN et al., 2013). Indirect losses are associated with flock devaluation and commercial barriers for transport of animals and germplasm, such as nannies, bucks, semen, and embryos (PINHEIRO et al., 2001;MODOLO et al., 2003).
Among the clinical presentations of lentivirus infections, arthritis is usually described for the CAE, which is more frequently observed in animals older than eight months old (CRAWFORD; ADAMS, 1981). Joint lesions may impair regular grazing leading to weight loss and incapacitating bucks of performing natural mating (PINHEIRO et al., 1999). Other studies demonstrated the increase in the joint size of SRLV infected animals (JUTILA, 1987;BRODIE et al., 1998;GREENWOOD, 1995;PINHEIRO et al., 2005;ABREU et al., 2010).
The respiratory clinical presentation is commonly observed in sheep with MV disease. A study performed in Spain showed that the main source of sheep discard was due to respiratory and neurological conditions (BENAVIDES et al., 2013). Reinstating this fact, infected animals were estimated to be discarded a year earlier than healthy animals (PETERHANS et al., 2004). The early loss of young animals causes an economic impact considering that one to three year-old animals present the best performance in production and cannot be easily replaced (PEREZ et al., 2010). According to Snowder et al. (1990a), sheep with subclinical infection by MVV do not present economic effects in wool production.
The effects in the mammary gland are the most important, considering that they affect milk production and predispose animals to secondary infections in this organ (SMITH; CUTLIP, 1988). Lentivirus infections may cause diffuse hardening of the mammary gland, even when microbial pathogens are not isolated from milk (BOHLAND; D' ANGELINO, 2005). LARA et al. (2005) consider interstitial mastitis a marked, hardening and frequent condition in dairy goat flocks. In addition, BENAVIDES et al. (2013) observed alterations in the mammary gland of dairy sheep diagnosed with MV, such as moderate to severe infiltration of lymphocytes, macrophages and plasma cells in the glandular parenchyma, as well as periductal hyperplasia of lymphoid follicles.
In general, seronegative sheep for MVV tend to produce more milk than seropositive sheep (SNOWDER et al., 1990b). The same occurs with goat nannies infected by CAE, which present a decrease in milk production and are more affected by health issues, besides reproductive problems. According to GREENWOOD (1995), seropositive multiparous goats presented an average reduction of 88 kg of milk production and 21 days of production in lactating period when compared with seronegative goats.
Other studies also identified a reduction in the milk production of dairy goats positive for SRLV, as observed by KRIEG; PETERHANS (1990), in which a decrease of approximately 10% was identified. BOHLAND; D'ANGELINO (2005) compared positive goat flocks with negatives and verified a reduction of 37 days in the lactating period and 94.6 L (21.5%) in total milk production per lactation. Moreover, a study performed with dairy goat flocks in a semi-arid region of Ceará, Brazil, reported an even higher reduction of the milk production estimated in 26% (BRITO, 2009). Based on MARTÍNEZ-NAVALÓN et al. (2013), milk production in seropositive animals decreases with the increase of age.
In the environmental conditions of the semi-arid region in Ceará, Brazil, CAE may cause significant losses in the income of milk production by mixed-breed goats. A loss in milk production of 20 infected animals in the 210 days of lactation was R$ 938.28 -406 €. Due to the low profit margin in milk production, the losses caused by disease may compromise profitability in the dairy goat production (CARNEIRO et al., 2011).
In addition to milk production, some studies demonstrate that a reduction in milk quality occurs and levels of fat, protein, lactose and total solids may be reduced. Some physical factors such as electroconductivity and chloride contents are higher in the milk of infected goats. Moreover, there is an increase in the somatic cell count (SMITH;CUTLIP, 1988;SANCHEZ et al., 2001;BIRGEL JUNIOR et al., 2007;BRITO, 2009;MARTÍNEZ-NAVALÓN et al., 2013).
Corroborating with the referenced literature, KABA et al. (2012) concluded that the milk of infected goat nannies has low levels of total protein (3.40 versus 3.35%, p ≤ 0.01), fat (3.69 versus 3.54%, p ≤ 0.01) and lactose (4.30 versus 4.25%, p ≤ 0.01). However, BRITO (2009) verified a 5% reduction in fat levels and 3% in total solids of seropositive goat milk and an increase of 32% in somatic cell count. TURIN et al. (2005) evaluated CAE effects in the production and biochemical components of milk produced by primiparas goat nannies and verified that milk production was similar among seropositive and seronegative individuals, and there was no significant difference in lactose values. However, levels of fat, protein and somatic cell count were statistically different. These studies indicate that the infection may interfere in milk quality, which might affect the production of dairy products. CARNEIRO et al. (2011), after studying the effects of SRLV in dairy goat flocks, evaluated the influence of the disease in parasite infection and verified that goat nannies from seropositive group needed deworming more frequently than seronegative females, which were more intense at the end of rainy season and in peripartum. Gastrointestinal parasite infection associated with CAE elevated 60% of the costs with deworming drugs, and primiparas were mostly affected. Seropositive group presented higher cost values related to anthelmintic drugs and laborin €$ 29.60 and €$ 34.53, respectively, when compared with the seronegative group. The authors concluded that such disease predisposes animals to gastrointestinal parasite infections; therefore, they raise costs of production with CAEV infected animals.
Infected animals are more susceptible to health issues than seronegative animals, such as peripartum udder edema, mastitis and enlargement of carpal joint, in addition to altered reproductive parameters. According to GREENWOOD (1995), among multiparous goat nannies, seropositive animals presented a higher rate of reproductive failure (43%) in comparison with seronegative ones (18%). However, there is no statistical difference in primiparas goat nannies. In the same study, the disease reduced in 5.6% the average weight of newborn goat kids.
The severe losses justify the control of lentivirus infections. Therefore, the application of prevention/control measures are suggested to minimize losses and promote optimal economic gain. Moreover, control measurements improve animal welfare, considering the obvious relation with disease and suffering (MURI et al., 2016). The use of control or eradication programs promotes decrease in seroprevalence to satisfactory levels and improves production and animal welfare consequently (PÉREZ et al., 2013).

CONSIDERATIONS ON CONTROL MEASURES
We suggest that disease control promotes improvement in milk production and quality, feed conversion and animal welfare, in addition to reducing costs with drugs and technical assistance. However, the producer should analyze the cost-benefit ratio for starting a program, considering that the necessary measures for control, and especially eradication, are expensive and laborious.
A major success in eradicating CAE was described in Japan, in which a series of measures against this disease was adopted between 2002 and 2006. The program used three strategies. Firstly, removal of goat kids immediately after birth; secondly, isolation of each generation; and thirdly, periodical discard of positive goats (AGID and PCR). After four generations, this set of measures promoted the transformation of infected goat flocks into CAEV-free and increased the milk production (KONISHI et al., 2011).
SRLV control is yet a problem for several producers due to the lack of communication regarding information generated by the scientific community to this audience. In addition, according to REINA et al. (2009), many countries have caprine and ovine populations with heterogeneous seroprevalence and a variety of breeds, environmental conditions and management particularities. Therefore, each country or region may need different control strategies. The situation in Brazil fits perfectly within this perspective. These issues prevent the implementation of a single political or control strategy as a reference that aims to minimize losses caused by lentivirus infections.

CONCLUSION
This study aimed to gather general aspects of SRLV, causative agents, and implications of these pathogens in the productive and economic aspects consequently. Although several studies have reported losses caused by SRLV, there is still a lack of data to assess the real costs for the application of control measures.  Brasil, 1987-1989. Arquivos da Faculdade de Veterinária da UFRGS, v.17, p.65-76, 1989. DAWSON, M. Pathogenesis of Maedi-Visna. The Veterinary Record, v.120, p.451-454, 1987.