Uterine Infections In Bovines
Dr. Omer din M.V.Sc (JRF -Gynaecology) ,ICAR NET - Gynaecologists, Veterinary polyclinic Barnala,Animal husbandry department,Punjab
The post-partum period is defined as the interval from parturition to complete uterine involution (return to an almost pre-partum stage). The severity of physiological, hormonal and nutritional stress faced by a pregnant animal results in several complications following parturition. Among them, post-partum uterine infection is one of the most important disorders in bovines, causing high economic losses due to prolonged days open and prolonged inter-calving intervals and infertility, resulting in involuntary culling . This has greater implications of animal welfare and economic impact on animal owner as well. Economic losses results from reduced reproductive performance, decreased milk yield, culling of infected animals from the herd, prolongation of the parturition-first insemination and parturition-conception intervals. Moreover, animals with uterine infection have lesser dry matter intake, feeding time, fewer aggressive interactions. Attempts to treat uterine infections using antibiotics lead to long-term secretion of residue in milk that effect public health negatively. It is thus amply evident that uterine infection not only has economic significance but also imparts negative effect on animal welfare and public health. The incidence rate of uterine infection in buffalo cows is reported to be much higher than in cows .The presence of pathogenic bacteria in the uterus causes inflammation, histological lesions of the endometrium, delays uterine involution and perturbs embryo survival in the subsequent conception .In this review, a summary of uterine infections in bovines, incidence, classifications,risk factors, prediction,diagnosis procedure and treatment option are described
Incidence
Subclinical endometritis is the most common uterine infection with incidence rate of 30% in lactating dairy cows, with the prevalence ranging from 11 to >70% in some herds. Metritis and clinical endometritis occur at incidence rate 20% in dairy cattle. In India incidence of uterine infections is much higher in buffalo then cattle. Incidence of endometritis and metritis is 30% and 24% respectively in buffalo. Higher incidence of uterine infection may be due to wallowing habitat or due to malpractice to inert hand or tail into vagina for letdown of milk.
Classification
Though numerous investigators have attempted classification of uterine infections based on clinical signs and severity of infection, but classification provided by Sheldon and others (2006) is most widely accepted because of its clear clinical definition of uterine infections. These diseases share common etiological factors, predispose to one another, and largely share common treatment. The five types of uterine infections defined by them are
Clinical metritis is defined as animal with an abnormally enlarged uterus with purulent uterine discharge detectable in the vagina within 21 days after parturition but without any signs of systemic illness
Clinical endometritis is presence of purulent (>50% pus) uterine discharge detectable in the vagina 21 days or more post-partum or muco-purulent (approximately 50% pus, 50% mucus) discharge detectable in the vagina after 26 days post-partum characterized by increased interval from calving to conception without any signs of systemic illness. Endometritis, involves only the endometrium and the underlying glandular tissues whereas metritis involves the endometrium, the underling glandular tissues and the muscular layer
Subclinical endometritis is inflammation of endometrium characteristic by higher number of neutrophils in uterine cytology without any purulent material in the vagina.
Pyometra is the accumulation of purulent material within the uterine lumen with persistent corpus luteum.
Puerperal metritis defined as an animal with an abnormally enlarged uterus and a fetid watery red-brown uterine discharge with signs of systemic illness (decreased milk yield, dullness or other signs of toxemia) and fever >39.5˚C within 21 days post-partum.
Risk Factors
The factors which predispose the animals to uterine infection are many
1. Retained fetal membranes (RFMs)
RFMs act as a good media for bacterial multiplication and bacterial toxins also slower the involution rate which predispose the animal to develop uterine infection. RFMs cause 50% cases of metritis in dairy animals.
2. Dystocia
Any external assistance to an animal with dystocia often results in damage to the uterine wall, creating wounds, which later are invaded by pathogens and result in uterine infection. Dystocia also result in a reduce daily dry matter intake in postpartum cows and thus a loss of weight with a higher risk for uterine infection.
3. Nutritional risk factor
Hypocalcaemia, hypoglycemia and deficiency of minerals are important risk factor for uterine infection.
Hypoglycemia or Negative energy balance
During puerperal period (just before and after calving) dams consume lesser dry matter intake, an after effect of higher glucocorticoids and increasing oestrogen in blood.This is in contrast to animal requiring required more energy for milk production. The disbalance in lesser energy intake and more loss through milk results in a condition called as negative energy balance (NEB). This leads to generation of NEFA (non-esterified fatty acids) and BHBA (Beta hydroxyl butyric acid) due to migration of fat from other tissue of the body toward the liver for generation of energy. Higher BHBA/NEFA and lower glucose level in blood during NEB affect chemotaxsis and phagocytosis activity of neutrophils. This is the reason that animals under negative energy balance have more chance to develop uterine infection.
Hypocalcaemia
Particularly subclinical hypocalcaemia after calving result lower muscular tone of uterus, which delay involution rate, hence more chances of developing uterine infection. Hypocalcaemia also inhibits the activation of neutrophils. Deficiency of vitamin E or selenium after calving also predisposes animals to develop uterine infection.
4. Environment hygiene
Dirty beddings, unhygienic calving room and obstetrical instrument leads to development of uterine infection.It is, therefore important that higher standard hygienic practices must be followed during calving.
5. Genetic selection
Cross breeding have lesser chance to develop uterine infection than pure breeds as in cross breeding there is lesser chance of dystocia and RFM as compared to the pure breeding.
6. Inaccurate heat detection
Under the influence of progesterone during non-heat period, uterine immune defense mechanism is suppressed, mostly due to greatly reduced blood supply to the uterus. This result in lesser PMNs and greater concentrations of immunosuppressant proteins in lumen of uterus.Therefore, inaccurate heat detection and subsequent insemination in luteal phase (progesterone dominant phase) cause development of uterine infection.
7. Age and parity
Old animals have more chance to develop uterine infection because of slow rate of involution and loss of body condition during transition period.
Prediction Of Uterine Infection
Advancement in science has allowed us the luxury of predicting chances of development of uterine infection by using some marker in blood or in uterine flushing. They are
1. Cytokines
Cytokines are a diverse group of non-antibody proteins that act as mediators between cells, whichare released in response to inflammation.Animal, which develop uterine infection after calving, has higher level of interleukin-10 (a type of cytokine) 15 days before calving, remaining high until 15 days post-partum.
2. Acute phase protein
These are glycoprotein, which are synthesized in response to the interleukin by liver during inflammatory condition. Animals, which develop uterine infection after calving, have higher level of haptoglobin and serum amyloid A in plasma and uterine flushing immediately after calving.
3. Change in BCS(Body Condition Score)
Cow should neither be overfeed nor underfeed before calving and during transition period (after calving).Body condition score more than 4 or lesser than 3 (on a scale of 1 - 5) before calving or during transition phase is more associated with uterine infection.
4. Non esterified fatty acids
Elevated concentration of Non esterified fatty acids (NEFA) indicate that animal is under negative energy balance which is detrimental to neutrophil functions and uterine health. 7 day before parturition NEFA concentration ≥0.6 mmol/L result 1.6 times more development of metritis.
Pathogenesis Of Uterine Infection
Even after normal calving calf-bed in most of the animals is contaminated with bacteria as necrotized caruncles, blood and cell debris provides a perfect medium for bacteria to grow. In majority, contaminants are eliminated during the first 6 weeks of postpartum. Only in those animals, which fail to expel contaminants/bacteria, uterine infection develops. Whether or not the bacteria are eliminated depends on the involution rate, uterine contractions, bacterial load, virulence of the organisms present, endometrial regeneration and defense mechanisms such as leukocyte migration, phagocytosis and inflammatory mediators. Uterine defense mechanism against the contaminant bacteria is maintained by polymorphonuclear inflammatory cells (PMNs), humoral antibodies, simple or pseudostratified columnar epithelium covering the endometrium and chemically by mucus secretions from the endometrial glands.
Disruption of these mechanisms allows opportunist pathogens to cause uterine infection. Higher bacterial load due to RFMs, dystocia or depression in the cow’s immune status due to higher progesterone in blood circulation and negative energy lead to establishment of infection. Escherichia coli, Streptococci, Arcanobacterium pyogenes, Bacillus licheniformis, Prevotella spp , Fusobacterium necrophorum and Staphylococci spp are bacterial species which can be isolated from uterus upto 6 week post-partum. Among these bacteria E.coli, A. Pyogenes, F. necrophorum and Bacteroides melaninogenicus species (pathogenic species) are most commonly associated with uterine infection. Arcanobacterium pyogenes and F. necrophorum promote each other’s growth by providing mutually favorable environment. Reduced oxygen reductase potential in uterus during infection either due to metabolism by bacteria (E.coli, A. pyogenes ) or oxygen consumption by neutrophils favor the growth of F. necrophorum and Bacteroides melaninogenicus ( anaerobic bacteria). Bacterial growth and bacterial metabolic product cause severe damage to endometrium and result in infertility.
Diagnostics Procedures
1. Clinical signs and history
Clinical signs vary according the type and severity of infection,like in clinical endometritis there is muco-purulent discharge at 26 days post-partum. In toxic puerperal metritis,there is brownish watery fetid discharge along with systemic illness. In herd history there will be increased first service conception rate, calving to conception interval and culling rate due to failure to conceive.
2. Recto-genital palpation
Recto-genital palpation helps diagnosis of pyometra and metritis. In pyometra, uterus is enlarged with thickened uterine wall. Diagnosis of clinical and subclinical endometritis using recto-genital palpation is subjective, not effective and prone to error as it lacks standardization.
3. Ultrasonography
In this method, endometrial thickness and ecogenicity of uterine fluid are checked. Endometrium becomes thicker with presence of anechoic fluid inside the uterus in severe infection like metritis, pyometra. In endometritis thickness of endometrium become more then 8mm.
4. Vaginal examination
Vaginal examination can be done by three methods viz. vaginoscope, metricheck and gloved hand.Vaginoscopeis inserted into the vagina of animal to check the presence of pus around the external cervical os or in the cranial vagina, presence of pus indicate uterine infection. Mucus or vaginal discharge which is collected by metricheck or by gloved hand can be classified as given below (Sheldon et al.,2006).Higher is score of vaginal discharge more severe is infection
Table 1.Classification of vaginal discharge collected by metricheck or by gloved hand method
| score 0 | Clear or translucent mucus |
| score 1 | Mucus containing flecks of white or off-white pus |
| score 2 | Discharge containing >50% white or off-white muco-purulent material |
| score 3 | Discharge containing > 50% purulent material, usually white or yellow, but occasionally sanguineous |
5. White side test
Cervical mucus is mixed with equal volume of 5% NaOH and heated up to the boiling point. Development of yellow color is indicative of positive reaction/uterine infection.
6. pH of cervical mucus
Alkaline pH (>8.0)of cervical mucus is indicative of uterine infection.
7. Uterine biopsy
Uterine biopsy is consider as gold standard diagnostic method for endometritis which is characterized by mild to moderate neutrophil and lymphocyte infiltration in lamina propria, epithelial disruption, degeneration and necrosis in epithelial cells of some endometrial glands.
8. Endometrial cytology
Method for obtaining endometrial cytology include cytobrush method, swab method and low volume lavage method. In cytobrush method,slides are made after taking cytobrush sample from dorsal wall of uterus,stained with giemsia stain, and observed under microscope for neutrophils number (PMN-Polymorphonuclear cells). Criteria for the diagnosis of subclinical endometritis using cytobrush method based on percentage of PMN present in the smear given by Sheldon et al.,2006.
Table 2.Citeria for diagnosis of subclinical endometritis using percentage of PMN in cytobrush method
| Days after Calving | Percentage PMN in cytology sample |
|---|---|
| 21-33 | >18% |
| 34–49 | >10% |
| >50 | >5% |
Treatment Of Uterine Infection
Uterine infection is a condition, which requires immediate intervention. There are several line of therapeutics which can be attempted. They are broadly classified into hormonal, antimicrobial and immunomodulation therapy. Choice of therapy depends upon severity of infection. A ideal therapy must be economical, don’t interferes uterine deference mechanism, have lesser withdrawal period in meat and milk and have lesser frequency of administration.
1. Hormonal therapy
The objective of hormonal therapy in resolving uterine infection is to induce estrus to increase estrogen level.
Prostaglandins and its analogues
Prostaglandins (PGF2α) cause luteolysis of corpus luteum, thereby decreasing progesterone concentration. This has cascading effect on stimulating uterine defence mechnanism. Moreover, PGF2α stimulate myometrial contractions which in turn expel debris and microorganisms from the uterus.PGF2a natural preparation (Dinoprost 25mg I/M) or synthetic preparation ( Cloprostenol 500ug I/M) can be used in uterine infections.
Estrogens
Estradiol is used for treatment of uterine infections as it stimulates myometrial contractions, increase phagocytosis of immune cells and mucus production by the reproductive tract.Estrogens at the dose rate of 3mg (estradiol) in mild to moderate uterine infections as intra muscular injection or administration of oxytocin 10-20 units 4 to 6 hours after injection of estrogens are useful.Excessive use of estrogen in the post-partum cow could lead to development of cystic ovarian degeneration. Residues of estrogens remain high in milk and meat for many days after use that could be detrimental to public health.
2. Antibiotic therapy
In severe infections antibiotic must be used parenterally or systemically as infected uterus have low oxygen tension, antibiotic-degrading enzymes, muco-purulent discharge, and organic debris could lead to poor efficacy of certain antimicrobial agents infused into uterus. Systemic treatment also provides better drug distribution to all layers of uterus and prevents iatrogenically induced contamination and injuries to uterine endometrium.Ceftiofur hydrochloride (2.2mg/kg I/M), Gentamicin (5mg/kg I/M), Tetracyclines (9-11 mg/kg I/V) and Ampicillin (4-6 mg/kg I/M) can be used.
3. Immunomodulation therapy
Immunomodulation is based on the principle that administration of immunomodulator leads to increase in uterus immunity by stimulating migration of leucocytes which clear the uterine infection.These are effective in the treatment of the subclincal endometritis but ineffective in severe infection due to presence of pus.
E.Coli lipopolysaccharides (LPS)
100ug LPS of E.coli Serotype 026:B6 (10000 endotoxin units/mg) in 20-30 ml NSS intrauterine cure subclinical endometritis on next estrus.
Levamisol
Levamisol which is a antinematodal can be used as immunomodulator @2.5mg/kg Bwt parenterally.
Oyster glycogen
Variable concentrations of oyster glycogen between 0.1 to 10 % in 60 mL of NSS can be used intrauterine.
Autologous plasma
50-100 mL of autologus plasma can be given by intrauterine route for 3 days.
Other immunomodulator
Leukotrine B4,LydiumKLP can also be used in uterine infection.
4. Other alternative treatment
Homeopathic drug utrogen 105ml gives good result for treatment of endometritis and harmone regulator. 5ml morning and evening.
Prevention
- Calving room,equipments must be properly clean.
- Give palatable energy rich diet like concentrate, molasses etc. immediately after calving.
- Breed at proper age (22 month) and weight (250-280kg) to avoid dystocia.
- Give Vitamin E (500mg) and selenium(150mg) injection one week before calving.
- Give calcium (50 mL/ daily) orally to high yield animals after calving.
- AI must be done under hygienic condition at proper time.
- Give light exercise and proper nutrition to advanced pregnant cattle to prevent excessive weight.
- Take pearl millet grain(2 kg), methi seeds(100g),asalio (50 g), soya (25 g) and jaggery(500 g) boil all these in water for one hour. Feeding of this mixture to cattle after delivery will help removing uterine infection.
Conclusion
Uterine infections are a major concern for dairy farmers in India. Although all types of uterine infections are injurious to animal health, subclinical endometritis requires attention as absence of any tell-tale signs causes decreased conception rate without any attempt of the farmer for its treatment. Different marker in blood like cytokine and acute phase protein can be used to identify animals, which are at greater risk to develop uterine infection.It is imperative for the farmer that uterine infections are diagnosed and treated early to reduce their impact on subsequent fertility of the animal.
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