Hypovitaminosis A coupled to secondary bacterial infection in beef cattle
- Xiuyuan He†1Email author,
- Yongtao Li†2,
- Meng Li3,
- Guangmin Jia2,
- Haiju Dong1,
- Yanru Zhang1,
- Cong He1,
- Chuanqing Wang1,
- Lixin Deng1 and
- Yurong Yang1
© He et al.; licensee BioMed Central Ltd. 2012
Received: 24 May 2012
Accepted: 22 August 2012
Published: 14 November 2012
Vitamin A is essential for normal growth, development, reproduction, cell proliferation, cell differentiation, immune function and vision. Hypovitaminosis A can lead to a series of pathological damage in animals. This report describes the case of hypovitaminosis A associated with secondary complications in calves.
From February to March in 2011, 2-and 3-month old beef calves presented with decreased eyesight, apparent blindness and persistent diarrhea occurred in a cattle farm of Hubei province, China. Based on history inspection and clinical observation, we made a tentative diagnosis of hypovitaminosis A. The disease was confirmed as a congenital vitamin A deficiency by determination of the concentrations of vitamin A in serum and feed samples. Furthermore, pathological and microbiological examination showed that the disease was associated with pathogenic Escherichia coli (E. coli) infection and mucosal barriers damage in intestines. The corresponding treatments were taken immediately, and the disease was finally under control for a month.
To our knowledge, this is the first report of hypovitaminosis A coupled to secondary infection of E. coli in beef cattle, advancing our knowledge of how vitamin A affects infection and immunity in animals. This study could also be contributed to scientific diagnosis and treatments of complex hypovitaminosis A in cattle.
KeywordsVitamin A Hypovitaminosis A Calves E. coli
Vitamin A is well known to be important for animal growth, development and various physiological processes, such as keeping the normal sight and bone function, especially in neonatal and growing animals . Vitamin A is not synthesized by vertebrates and depends essentially onβ-carotene of green plants in dietary provision . Since the discovery of vitamin A in 1920s, cases have been reported frequently about hypovitaminosis A in animals [3, 4]. Many studies have showed that hypovitaminosis A can lead to a series of pathological damage, such as growth stunting, reproductive dysfunction, and low immunity, epithelial keratinization and degeneration, xerophthalmia and night blindness [5–7]. Researchers also demonstrated that vitamin A deficiency can be harmful for protein synthesis and maintenance of normal growth and metabolism, and decrease the body resistance to infection [8, 9]. For grazing animals, vitamin A deficiency occurred easily in spring or winter when it lacks of green feed. To date, several investigations have been conducted on vitamin A deficiency in cattle [10–13]. In humans, there has been reported that vitamin A decreased during the acute phase response to bacterial infection . However, the case of vitamin A deficiency in beef calves accompanied by bacterial infections has not yet been reported. In this study, we report on an investigation of vitamin A deficiency with E. coli infection in beef calves, a systematic diagnostic and effective treatment programs conducted on a beef cattle farm, which could be contributed to scientific prevention and control of vitamin A deficiency in cattle.
In Suizhou of Hubei Province, there is a beef cattle farm with a total of 553 cattle, including 144 cows, 66 pregnant cows, 59 calves and 284 finishing cattle. From February to March in 2011, the symptoms of elevated body temperature, loss of appetite and blurred vision were detected in 12 calves at the age of 2- to 3-month and 4 calves were total blind in April. The cows which produced calves last year could be found mainly lower abdomen edema with 10% morbidity, and 6 of 13 newborn calves appeared illness with 46% morbidity. The cattle diet included 0.5 to 1 kg concentrate feed (53% maize, 18% soybean meal and 29%wheat bran), 3.5 to 5 kg straw, and 15 kg (fresh weight) white lees, without any additives.
The earliest changes of all affected calves were anorexia, slow growth and weakness. Though clinical signs of affected calves varied, the common presence included mild to severe ataxia, partial blindness or total blindness as judged by avoidance of obstacles, rumen distention and persistent diarrhoea. Even in bright sunlight, some affected calves also lost light reflex. There was also absence of the blink response or eye preservation reflex. Compared to normal cattle, all affected calves had significantly increased defecography and urination. Examination of the eye revealed a dilated and circular pupil in affected calf, but horizontal and oval one in the normal.
Determination of the content of vitamin A and aflatoxin B1
Vitamin A concentration in different samples from clinically affected calves compared to reference values
Normal value (16)
Moreover, in the cattle farm of China, aflatoxin B1 is the most common aflatoxin and the necessary inspection item in feed. In order to verify whether the disease was related to aflatoxin poisoning, we also measured the aflatoxin B1  and found that the concentration was 8.3 μg/kg in feed far less than the lowest poisoning dose of 100 μg/kg , indicating that the disease was not associated with aflatoxin B1 poisoning.
Biochemical properties of the bacterial colonies isolated from intestine and rectal swabs of affected calves
Pathological and microbiological findings from five affected calves
E. coli serotypeb
MLD50 for E. coli (CFU)c
intestine, rectal swabs
5.45 × 109
intestine, rectal swabs
intestine, rectal swabs
The antibiotic sensitivity test of E. coli strains isolated from affected calves
Considering the above clinical findings and experimental tests, we took the following measures to treat and control the disease. Firstly, to the affected calves, it is effective for controlling vitamin A deficiency through repeated intramuscular injections of vitamin A or continuous dietary supplementation. The affected cows and calves were intramuscularly administered by vitamins A for a month at the dose of 200000 IU once per day and 50000 IU respectively. Additionally, the severe affected cows and calf was orally treated respectively by 30 ml and 2 ml cod liver oil each day for a month. Secondly, antibacterial drugs, such as amoxicillin, ciprofloxacin and gentamicin were used to control secondary infection of E. coli. Last but not the least, calcium gluconate or glucose and mannitol were intravenously injected to alleviate cerebral edema and intracranial pressure, which contributes to reduce the neurological symptoms of the affected cattle. After one and a half months for treatment, most of mildly affected calves had a recovery of sight and the secondary E. coli infection was also effectively controlled. However, two calves with severe signs were totally blind in the end. In brief, the effect of corresponding treatments confirms also that the disease was attributed mainly to hypovitaminosis A.
Vitamin A of grazing animals is totally dependent on exogenous supply. According to previous studies, the minimum requirement of vitamin A in cow is about 30 IU/kg each day, and the demand should be increased by 50% during lactation and pregnancy . The long-term lack of dietary vitamin A or carotene in cow can easily result in hypovitaminosis A in newborn calves . The rapid growth and development of calves need enough vitamin A, through liver storage and extra implements, mainly dependent on breast milk. However, in our current study, beef cattle were fed with rice straw and distillers’ grains for a long time, without green feed, carrots and other vitamin A-rich feed, which resulted in vitamin A deficiency in pregnant and lactation cows. Under normal circumstances, the content of vitamin A in the cattle feed should not be less than 400,000 IU/kg in order to ensure normal growth and development. However, the vitamin A content was 1360 IU/kg in feed of this farm. In the serums of affected calves, the average content of vitamin A was 130 IU/L at the late stage in this farm, far below the normal value , confirming this disease was related with vitamin A deficiency in calves.
The blindness disorders are regarded as the typical signs in affected calves of vitamin A deficiency [21, 22]. The mechanisms of blindness due to vitamin A deficiency have been explored for many years. In terms of blindness or associated signs, fundus examination plays an important role in the quick diagnosis of hypovitaminosis A. At the early stage of hypovitaminosis A, papilledema is the first sign of changes in the optic disc and is reversible under the experimental conditions. The most representative characteristic, however, is pigmentation with various sizes and shapes on the tapetum nigrum of retina. In this study, no clear papilledema was found, which might be due to the delay of taking photos of fundus. However, the irregular pigmentation was found clearly with varied sizes at local areas in the tapetum nigrum and tapetum lucidum, especially in tapetum nigrum (Figure 1).
Vitamin A plays a significant role in immune system function of animals. In humans, it is well accepted that `vitamin A deficiency impairs innate immunity by impeding normal regeneration of mucosal barriers damaged by infection, and by diminishing the function of immune cells [23, 24]. In the case of diarrheal diseases, vitamin A could promote regeneration of damaged mucosal epithelium and enhance the phagocytic activity of neutrophils and macrophages. It has also been shown that vitamin A can reduce the incidence and duration of diarrhea in children [25, 26]. In this study, based on the clinical findings, his-pathological changes in intestines and vitamin A determinations, we could conclude that hypovitaminosis A impeded mucosal barriers of intestines and lowered the immunity of cattle which made the cattle more susceptible to E. coli, and the intractable diarrhea of cattle was likely attributed to both hypovitaminosis A and pathogenic E. coli infections, which was in accordance to previous studies [27, 28]. Therefore, the corresponding treatment should include vitamin A supplement and antibacterial drugs utilization according the antibiotic susceptibility test. It is intriguing that Rumen distention was present in affected calves, whether it is due to hypovitaminosis A or E. coli infections remains further studies. Further research on E. coli isolates should be performed to identify genetic material encoding for specific virulence factors of E. coli and to demonstrate the effect of vitamin A deficiency on expression of innate immunity-related genes and development of immune cells in gastrointestinal tract of cattle .
This report describes a predominant case about hypovitaminosis A coupled to secondary E. coli infection in beef calves. Based on the clinical signs and experimental tests, corresponding measures were taken immediately to make vitamin A recovery at the normal level and to control E. coli infection in intestines of calves. Collectively, the findings provided insights into the important role of vitamin A in the immunity against microbiology infections of animals.
Orally informed consent was obtained from the owner of cattle farm for publication of this case report and any accompanying images.
- (E. coli):
High-Performance Liquid Chromatography
Fifty percent mouse lethal dose.
The authors would like to thank PhD. Li Yuan for her contribution to antibiotic test experiments, Yongqiang Cao for his help in clinical examination, and Pro. Yanxiu Liu and Wendy Barclay for critically reading the manuscript. The study was supported by National beef cattle industry research system (CARS-38).
- Clagett-Dame M, Knutson D: Vitamin A in reproduction and development. Nutrients. 2011, 3 (4): 385-428. 10.3390/nu3040385.PubMed CentralView ArticlePubMed
- Oldham ER, Eberhart RJ, Muller LD: Effects of supplemental vitamin A or beta-carotene during the dry period and early lactation on udder health. J Dairy Sci. 1991, 74 (11): 3775-3781. 10.3168/jds.S0022-0302(91)78569-X.View ArticlePubMed
- Booth A, Reid M, Clark T: Hypovitaminosis A in feedlot cattle. J Am Vet Med Assoc. 1987, 190 (10): 1305-1308.PubMed
- Carrigan MJ, Glastonbury JR, Evers JV: Hypovitaminosis A in pigs. Aust Vet J. 1988, 65 (5): 158-160. 10.1111/j.1751-0813.1988.tb14449.x.View ArticlePubMed
- De Risio L, Beltran E, de Stefani A, Holloway A, Matiasek K: Neurological dysfunction and caudal fossa overcrowding in a young cheetah with hypovitaminosis A. Vet Rec. 2010, 167 (14): 534-536. 10.1136/vr.c4802.View ArticlePubMed
- Clagett-Dame M, DeLuca HF: The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr. 2002, 22: 347-381. 10.1146/annurev.nutr.22.010402.102745E.View ArticlePubMed
- Gallina AM, Helmboldt CF, Frier HI, Nielsen SW, Eaton HD: Bone growth in the hypovitaminotic A calf. J Nutr. 1970, 100 (1): 129-141.PubMed
- See AW, Kaiser ME, White JC, Clagett-Dame M: A nutritional model of late embryonic vitamin A deficiency produces defects in organogenesis at a high penetrance and reveals new roles for the vitamin in skeletal development. Dev Biol. 2008, 316 (2): 171-190. 10.1016/j.ydbio.2007.10.018.View ArticlePubMed
- Stephensen CB: Vitamin A, infection, and immune function. Annu Rev Nutr. 2001, 21: 167-192. 10.1146/annurev.nutr.21.1.167.View ArticlePubMed
- Donkersgoed JV, Clark EG: Blindness caused by hypovitaminosis A in feedlot cattle. Can Vet J. 1988, 29 (11): 925-927.PubMed CentralPubMed
- Hill B, Holroyd R, Sullivan M: Clinical and pathological findings associated with congenital hypovitaminosis A in extensively grazed beef cattle. Aust Vet J. 2009, 87 (3): 94-98. 10.1111/j.1751-0813.2009.00398.x.View ArticlePubMed
- Millemann Y, Benoit-Valiergue H, Bonnin JP, Fontaine JJ, Maillard R: Ocular and cardiac malformations associated with maternal hypovitaminosis A in cattle. Vet Rec. 2007, 160 (13): 441-443. 10.1136/vr.160.13.441.View ArticlePubMed
- Puvogel G, Baumrucker C, Blum JW: Plasma vitamin A status in calves fed colostrum from cows that were fed vitamin A during late pregnancy. J Anim Physiol Anim Nutr. 2008, 92 (5): 614-620. 10.1111/j.1439-0396.2007.00757.x.View Article
- Stephensen CB, Gildengorin G: Serum retinol, the acute phase response, and the apparent misclassification of vitamin A status in the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 2000, 72 (5): 1170-1178.PubMed
- Suzuki J, Katoh N: A simple and cheap methods for measuring serum vitamin A in cattle using only a spectrophotometer. Nihon juigaku zasshi. 1990, 52 (6): 1281-1283. 10.1292/jvms1939.52.1281.View ArticlePubMed
- Wang J: "Veterinary Internal Medicine (4th) Edition". 2010, Beijing: China Agricultural Press, 178-181.
- Stroka J, Petz M, Joerissen U, Anklam E: Investigation of various extractants for the analysis of aflatoxin B1 in different food and feed matrices. Food Addit Contam. 1999, 16 (8): 331-338. 10.1080/026520399283902.View ArticlePubMed
- Rasostits OM, Gay CC, Blood DC, Hinchcliff KW: Veterinary medicine. 2000, London: W.B. Saunders Co. Ltd, 1684-1688.
- Kaneene JB, Warnick LD, Bolin CA, Erskine RJ, May K, et al: Changes in tetracycline susceptibility of enteric bacteria following switching to nonmedicated milk replacer for dairy calves. J Clin Microbiol. 2008, 46 (6): 1968-1977. 10.1128/JCM.00169-08.PubMed CentralView ArticlePubMed
- Hamilton MA, Russo RC: Trimmed Spearman-Karber method for estimating median lethal concentrations in toxicity bioassays. Environ Sci Technol. 1977, 11 (7): 714-719. 10.1021/es60130a004.View Article
- Mason CS, Buxton D, Gartside JF: Congenital ocular abnormalities in calves associated with maternal hypovitaminosis A. Vet Rec. 2003, 153 (7): 213-214. 10.1136/vr.153.7.213.View ArticlePubMed
- van der Lugt JJ, Prozesky L: The pathology of blindness in new-born calves caused by hypovitaminosis A. Onderstepoort J Vet Res. 1989, 56 (2): 99-109.PubMed
- Twining SS, Schulte DP, Wilson PM, Fish BL, Moulder JE: Vitamin A deficiency alters rat neutrophil function. J Nutr. 1997, 127 (4): 558-565.PubMed
- Thurnham DI, Northrop-Clewes CA, McCullough FS, Das BS, Lunn PG: Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants. J Infect Dis. 2000, 182 (Suppl 1): S23-S28.View ArticlePubMed
- Sircar BK, Ghosh S, Sengupta PG, Gupta DN, Mondal SK, et al: Impact of vitamin A supplementation to rural children on morbidity due to diarrhoea. Indian J Med Res. 2001, 113: 53-59.PubMed
- Barreto ML, Santos LM, Assis AM, Araujo MP, Farenzena GG, Santos PA, Fiaccone RL: Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil. Lancet. 1994, 344 (8917): 228-231. 10.1016/S0140-6736(94)92998-X.View ArticlePubMed
- Yang Y, Yuan Y, Tao Y, Wang W: Effects of vitamin A deficiency on mucosal immunity and response to intestinal infection in rats. Nutrition. 2011, 27 (2): 227-232. 10.1016/j.nut.2009.11.024.View ArticlePubMed
- Friedman A, Meidovsky A, Leitner G, Sklan D: Decreased resistance and immune response to Escherichia coli infection in chicks with low or high intakes of vitamin A. J Nutr. 1991, 121 (3): 395-400.PubMed
- Amit-Romach E, Uni Z, Cheled S, Berkovich Z, Reifen R: Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet. J Nutr Biochem. 2009, 20 (1): 70-77. 10.1016/j.jnutbio.2008.01.002.View ArticlePubMed