Date Published: June 10, 2019
Publisher: BioMed Central
Author(s): Ronja Mathiesen, Mariann Chriél, Tina Struve, Peter Mikael Helweg Heegaard.
Pre-weaning diarrhea (PWD) is a severe syndrome, with world-wide occurrence, affecting farmed mink (Neovison vison) kits during the lactation period. Kits affected by PWD often display clinical signs such as: yellow-white diarrhea, greasy skin, and dehydration. In severe cases the kits eventually die. It is common practice to treat PWD using antimicrobials; however the effect is not well documented. Due to the multifactorial etiology of PWD vaccine development is not feasible. The role played by the immune status of the mink kits with respect to their susceptibility to PWD is not well studied. To elucidate the possible association between PWD and total IgG serum concentration in young kits we analyzed blood collected from kits from 100 litters on two mink farms during the same breeding period, one farm being a case farm with high prevalence of PWD, and the other being a control farm with no cases of PWD.
Kits affected by PWD had a significantly reduced weight gain compared to unaffected control kits. Litters born later in the breeding period came down with PWD at an earlier age than litters born at the start of the breeding period. We found that PWD affected kits had significantly lower concentrations of serum IgG compared to unaffected kits at 13–15 days of age (the last blood sampling point of the study).
The results in this study suggest that PWD affected kits less efficiently absorbed IgG from maternal milk or had a lower intake of maternal milk, potentially contributing to the exacerbation of disease. A lower intake of IgG and/or less absorption from maternal milk could also pre-dispose kits for PWD. Future studies will be needed to elucidate if the circulating level of IgG is directly related to protection against disease and to investigate if administration of IgG could be helpful in alleviating and/or preventing PWD in mink kits.
A year on a mink farm in the Northern Hemisphere begins after pelting at the end of November and start December. Only mink selected for breeding continue on to the next year . Due to the photoperiod and climate of the Northern Hemisphere all mink come into heat once a year in March . Mink kits are born in late April to mid-May and after 4 weeks of lactation they start eating by themselves. During the lactation period antimicrobials are frequently used on the dams and/or kits, increasing the risk of antimicrobial resistance in bacteria [3, 4]. This increase in use of antimicrobials during the lactation period could be due to an increased incidence or increased awareness, and/or severity of pre-weaning diarrhea (PWD) [5, 6]. PWD is common on mink farms and the onset is usually around 1–4 weeks after parturition; however both morbidity and mortality varies between farms and breeding periods [7–9]. Finding clinical signs in more than 15% of the litters on a farm is considered a severe outbreak . Affected kits present signs such as; a profuse yellow/white foamy diarrhea, dehydration, greasy skin as a result of increased secretion from the cervical apocrine glands in the neck region, a red and swollen perianal region, and distressed vocalization [8, 11]. In severe cases, PWD can lead to dehydration and eventually death. Furthermore, kits affected by PWD have a lower body weight compared to age-matched healthy control kits . Because of the resource demanding consequences and economic losses associated with PWD a lot of interest has been directed towards understanding the syndrome and finding the specific cause in order to prevent or cure PWD. However, the syndrome is considered to have a multifactorial etiology, with no defined cause, and although some enteropathogens, including both bacteria and virus have been implicated, it has proven to be difficult to pinpoint specific pathogens of major significance for developing PWD [9, 13]. Some risk factors associated with PWD include; the birth date of the kits-with a higher risk associated with being born late in the breeding period , as well as the age of the dam with first year dams having a higher incidence of affected kits than second year dams [5, 7]. It has been shown by litter mixing experiments that the dam is an important factor in contracting PWD . The fact that older dams have a lower risk of getting kits affected by PWD could indicate that the maturity of the maternal immune system could be important and that bolstering the mink kits’ own immune system could be part of the solution. The predominant immunoglobulin found in mink milk is immunoglobulin G (IgG) . Mink kits are born with an immature immune system and with a very low serum concentration of IgG [14, 15]. It is vital for the kits that they absorb the IgG from the dams’ colostrum and milk after birth, which provides an defense system against a wide range of microbes and convey passive immunity until the mink kits start producing IgG by themselves 7–8 weeks after parturition . Mink kits are able to transfer IgG from the dams’ milk to the circulation until they are at least 47 days old [14, 16], which is in contrast to other farm-raised animals, like ruminants and pigs, where the gut-passage of IgG closes 24 h after parturition . The principle of passive immunization with antibodies delivered from mother to offspring has been demonstrated more than a 100 years ago . The protective effect of giving immunoglobulins towards bacteria to pigs [19, 20], and against virus to ferrets [21, 22] and mink kits  has been reported previously. The protective role of passive immunization by maternally transferred IgG with regards to PWD in mink kits has not been investigated previously. The objective of this study was to determine if there was an association between mink kit serum IgG concentration and the development of PWD.
The median kit body weight for both farms when the kits were 1 day old was 11.9 g (25th and 75th percentiles 11.0–13.2 g) on the control farm and 11.3 g (25th and 75th percentiles 9.5–12.8 g) on the case farm (n = 401 for both farms, Table 3). When the kits were 1–9 days old there was no significant difference observed in the median kit body weight between the case and the control farm (Fig. 1 and Table 3). However, the median body weight of the kits from the case farm was consistently different than that of the control farm from day 3 and onwards and this difference increased with the age of the kits (Fig. 1 and Table 3). The observed median kit body weight (Fig. 1) was significantly different between control (median 59.5 g, 25th and 75th percentiles 53.4–65.2 g) and case kits (median 57.4, 25th and 75th percentiles 46.0–65.2 g) when the kits were 11 days old (P < 0.05) and until the end of the sampling on day 15 (median on the control farm 88.5 g vs. 79.9 g on the case farm; P < 0.0001).Table 3Mink kit body weight results from the two farmsKit age (days)Control farmCase farmNo. weighed kitsMedian kit body weight (g)25th percentile (g)75th percentile (g)No. weighed kitsMedian kit body weight (g)25th percentile (g)75th percentile (g)140111.911.013.240111.39.512.8333418.516.320.534317.415.620.3532726.423.429.133125.222.729.87314126.96.36.199335.230.340.3930647.241.651.832145.437.053.31130659.553.465.231657.446.065.21330674.467.581.0307a65.953.777.015b30588.580.196.325679.966.089.6aKits in case litters (PWD affected) decreased after day 13bAll groups (1–4) on the control farm and groups 1–3 on the case farm were weighed until day 15, while group 4 on the case farm was weighed until day 13Fig. 1The median kit body weight of control (black columns) vs. case (white columns) mink kits. All groups (1–4) on the control farm and groups 1–3 on the case farm were weighed until day 15, while group 4 on the case farm was weighed until day 13. Statistical significance of differences between the two farms was determined by the Mann–Whitney U test (for nonparametric variables) (*P < 0.05; ****P < 0.0001). Bars indicate the median ± IQR Based on a previous observation on mixed litters in which kits moved from their original litter, which later got affected by PWD, developed PWD in the “new” litter, while the new littermates did not , we hypothesized that maternal factors may be important for the susceptibility of kits to PWD. One such potentially important factor could be maternal IgG and its efficiency of transfer from dam to offspring. In contrast to other farm-raised animals, like the ruminants and pigs, in which intestinal transport of IgG takes place only within the first 24 h after parturition , the mink kit intestine allows uptake of maternal IgG until 4–5 weeks after parturition . The kits’ own IgG production does not start until 7–8 weeks after parturition  and we therefore chose to study the maternally derived IgG in mink kit serum from birth until the kits were 13–15 days old. We have previously established that the serum IgG concentration in healthy mink kits reaches a constant level not differing much between kits at day 8 after birth and onwards . It is therefore assumed that there should be no significant difference between serum IgG concentrations at day 13 versus day 15 postpartum in healthy mink kits. PWD is still a large issue on many farms in fur-producing countries and as it is associated with a multifactorial etiology finding a possible cure/treatment is challenging. Our results show that the serum IgG concentration is lower in mink kits affected by PWD compared to the control kits, when they are 13–15 days old. This suggests that PWD-affected kits less efficiently absorbed IgG from maternal milk or had a lower intake of maternal milk as their weight was also lower compared to the control kits. This reduced uptake of milk IgG could potentially contribute to an exacerbation of the disease. Future studies will be needed to elucidate if the circulating level of IgG is directly related to protection against disease and to investigate if immunoglobulin supplementation could be helpful in alleviating and/or preventing PWD in mink kits. Source: http://doi.org/10.1186/s13028-019-0461-5