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Impact of treatment with anti-parasitic (Ivermectin)during prepartum period on mastitis andpostpartum reproductive e�ciency measurementsin Egyptian Baladi cowsAhmed Ismail Damarany  ( dr_damarana@yahoo.com )

Aswan University Faculty of Agriculture and Natural Resources https://orcid.org/0000-0002-0757-933X

Research Article

Keywords: Ivermectin, mastitis, postpartum reproductive e�ciency measurements, Baladi cows

Posted Date: August 23rd, 2021

DOI: https://doi.org/10.21203/rs.3.rs-823328/v1

License: This work is licensed under a Creative Commons Attribution 4.0 International License.  Read Full License

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AbstractThe current investigation was designed to determine the effect of treatment with anti-parasites(Ivermectin) on mastitis and postpartum reproductive e�ciency measurements in Egyptian Baladi cows.Twenty-four of the cows included in this study were split into two groups. The �rst group (n = 12 cows)was injected two months prepartum with two doses (15 days inter-treatment) of IVOMEC® Plus solutionsubcutaneously behind the shoulder, 1ml/50kg live body weight as prescribed by the manufacturer, whilstthe other group (n = 12 cows) was used as a control group. The present results revealed that the incidentrate of mastitis in treated cows’ group was signi�cantly (P < 0.05) lower (16.7%) than control cows’ group(41.7%). The conception rate in treated cows’ group was signi�cantly (P < 0.05) higher (66.7%) comparedwith (33.3%) in control group. The time from calving to conception in treated cows was signi�cantly (P < 0.05) lower 86.5 ± 11.4 days compared to 123.3 ± 13.2 days in the control group. The occurrence rate ofanestrous cases was signi�cantly (P < 0.05) lower (8.3%) in treated cows than (control group) (25%). Inconclusion, the current study indicates there is an association between treated cows with anti-parasites(Ivermectin) two months prepartum and incidence rate of mastitis addition an improvement in thereproductive performance in treated cows relative to untreated cows. Therefore, the current studyrecommends the herdsmen treats their cows with anti-parasites (Ivermectin) during the prepartum periodfor less mastitis incidence rate and better reproductive e�ciency.

IntroductionEndo-and ecto-parasites infestation causes high economic losses in livestock especially farm animals.Economic losses are represented by costs of anthelmintics drugs, higher mortality rate, decline in meat,milk, growth rate and fertility (Mendes et al., 2008). Economic loss was estimated by US $ 3.2 billion perannum worldwide due to liver worm (Fasciola) in livestock (Spithill et al., 1999). In Brazil Grisi et al (2014)reported that economic losses due to cattle external and internal parasite total loss nearly 14.0 million ofUS$ annual. Lawrence and Ibarbura (2007) estimated the economic losses of internal parasites(gastrointestinal nematode) control in beef cattle and reported that there was a 34% decrease in thebreak-even price for cattle that did not treatment by deworming. Mavrogianni et al. (2012); Mavrogianni etal. (2014) reported that there is a correlation between indo-parasitic infections and increased frequency ofclinical or subclinical mastitis during the �rst two weeks post-partum in ewes. FDA- was approvedIvermectin as broad spectrum anti-parasitic agent (Gonzalez Canga et al., 2008). Ivermectin is consideredto be a wonder drug due to its anti-parasitic activity against to each both internal and external-parasiticand has multiple applications in veterinary and human medicine (Geary, 2005; Crump, 2017; Sharun et al.,2019). Sajid et al. (2006); Jameel et al. (2015) reported that Ivermectin have immune-potentiating activityin cows. Yates and Wolstenholme (2004); Chaccour et al. (2013); Suarez et al. (2013) showed thatIvermectin is effectively and widely used against a lot of external and internal parasite. Pregnancy rateswere higher in cows after treatment with anti-parasitic drugs (Ivermectin and Eprinomectin) comparedwith non-treated cows (Loyacano et al., 2002; Kaley et al., 2019; Volk et al., 2019). Andresen et al. (2017)observed that marked improvement in reproductive performance of cow and heifers after administration

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of anti-parasites treatment compared to untreated controls group. Infected buffaloes with internalparasites (Fasciola) were need a long time from calving to conception (Seliem et al., 2010). Dairy cowswhich treated with anti-parasites need to less time to conception postpartum (Sanchez et al., 2002). Liver�uke infections (Fasciolosis) in cows were correlated by ovarian inactivity and other infertility problems(Ahmed, 2007). Recently ivermectin’s used as an antiviral because against effects towards a number ofRNA viruses including human immunode�ciency virus (HIV)-1 and SARS-CoV-2 (COVID-19) (Wagstaff etal. 2012; Caly et al., 2020; Kumar et al., 2020). There is little information, available to effect of treatmentwith anti-parasites on postpartum reproductive performance in Egyptian Baladi cows. In the light previousthe current investigation was planned to study the effect of treatment with anti-parasites (Ivermectin) onmastitis and postpartum reproductive e�ciency measurements in Egyptian Baladi cows

Materials And Methods

Climatic conditions and farm locationThe research performed in farm located in one of a village in Kom Ombou city (32̊, 31' 23" East and 22̊,28' 09" North), Aswan governorate. Average of the ambient temperature was (Min.12.3-22.1oC) and (Max.24.2-38.0oC), relative humidity (18–24) during the experimental period which extended from Septemberto April.

Management and feeding of herdTwenty-four of Baladi cows were used in the current research. Alfa- Alfa alongside the concentrate rationand hay wheat was offered to cows during the experimental period. Cows were used before two monthspre-partum after drying. Table (1) shows the speci�cations of experiment animals. The cows were kept intraditional farm conditions under semi shade system. According the farm routine work all of cows wereraise under the typical environmental and managerial conditions.

Design of the experimentThe cows were classi�ed into two groups ((n = 12 cows for each group). The �rst group (n = 12 cows) wastreated with two doses from IVOMEC® Plus (Ivermectin 1% w/v + clorsulon 10% w/v), while anothergroup (n = 12 cows) was used as a control group. The interval between the �rst treatments and thesecond was 15 days. The cows injected with IVOMEC® Plus solution subcutaneously (under the skin)behind the shoulder, 1ml/50kgBW as recommended by the manufacturer, this volume equivalent 10 mgIvermectin and 100 mg clorsulon. According to Mike Catangui (2016) IVOMEC® Plus drug used to as ananti endo or ecto-parasites (gastrointestinal roundworms, liver �ukes, lungworms, cattle grubs, suckingice, and mange mites). Table (2) clarify classi�cation of (Ivermectin + clorsulon) combination accordingto US FDA (Food and Drug Administration, 2015).

Detection of Heat and pregnancy diagnosis

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Daily visual observation for cows were performed for heat detection in the morning at 6:0 am. and 6:0pm, for sexual behavior sings exhibited. Just appearance standing behavior in the cows was matednaturally. Rectal palpation was used (after 60 days post-service), to diagnose the established pregnancy.

Mastitis diagnosisCows have acute or sub-clinical mastitis were diagnosis by (California Mastitis Test) and themanufacturing steps followed up

Sub-clinical mastitis: Cows considered to be infected by sub-clinical mastitis when cows did not displayany symptoms of mastitis, in each both milk and udder but mastitis is detected by a detector (CaliforniaMastitis Test) (Kathiriya et al., 2014).

Postpartum reproductive e�ciency determinationConception rate

estimated as the percentage of animals, that pregnant from the �rst service post-partum

Conception rate = Number of pregnant cows/Total number of served cows x 100

Days open

estimated as the time from parturition to conceived in cows

Postpartum ovarian dysfunction determinationAnestrous cases

Cows did not display any visible signs of estrus during = 60th day postpartum according to Kamal et al.(2012)

True anestrous case

Cows considered have true anestrous case when rectal check ovaries are smooth, small and inactive withthe absence of corpus luteum and plasma progesterone concentration remain in the basal levels(1ng/ml) blood (Kamal et al., 2012).

Blood samples and biochemical assayBlood samples (10 ml) were collected from cows in estrus, 7 and 21 days post estrus inter heparinizedtubes from the jugular vein. For plasma harvesting the samples were centrifuged at 3000 rpm for 20minutes. The separated plasma was stored under − 18 ºC until the time of analysis. Progesterone (P4)and estradiol-17β (E2) hormones were determined by radioimmunoassay kit (Immunotech, France).Progesterone and estradiol-17β sensitivity values were stated to be 0.03 ng/ml and 4.0 pg/ml,

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respectively according to manufacturer labeled information. Intra assay variation coe�cient was 6.2%and 12.2% for progesterone (P4) and estradiol-17β (E2), respectively.

Statistical analysisThe statistical design involved one factor (treatment effect) on mastitis and postpartum reproductivee�ciency measurements in cows. Chi-Square test was used to verify the signi�cance of percentagevalues. The statistical analysis was performed by Software (SAS, 2002). Following model was used:

Yij = µ + Ti + eijWhere:

Yij = the observation trait

µ = overall mean

Ti = effect of treatment (treated = 1 and untreated = 2)

eij = experimental error

Duncan’s Multiple Range test (Duncan, 1955) was used to check the signi�cance of the differencesbetween means.

Results

Effect of treatment with anti-parasites (Ivermectin) onoccurrence rate (%) of mastitis in Baladi cowsFigure (1) indicates the percentage of mastitis in treated cows’ group was signi�cantly (P < 0.05) lower(16.7%) than control cows’ group (41.7%).

Effect of treatment with anti-parasites (Ivermectin) on days open and conception rate (%) in Baladi cows

Table (3) illustrates that the time from calving to conceived in treated cows’ group was signi�cantly (P < 0.05) lower 86.5 ± 11.4 days than untreated cows (control group) 123.3 ± 13.2 days. Figures (2) showsthat the conception rate (%) in treated cows’ group was signi�cantly (P < 0.05) higher (66.7%) comparedwith untreated cows (control group) (33.3%).

Effect of treatment with anti-parasites (Ivermectin) onovarian dysfunction in Baladi cowsFigure (3) indicates that the proportion of anestrous cases (%) was signi�cantly (P < 0.05) lower (8.3%) intreated cows’ group than untreated cows (control group) (25%).

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Concentrations of progesterone and estradiol − 17β at estrus, 7- and 21-day post-service in treated anduntreated Baladi cows

Table (4) indicates that concentrations of progesterone and estradiol at the time of estrus weresigni�cantly (P < 0.05) higher in pregnant cows than non-pregnant. A signi�cant gradually increase in theconcentration of progesterone was showed from estrus to the next day's post-estrus in blood samples inpregnant cows compared to non-pregnant cows. Concentrations of estradiol-17β were recorded highlevels at day of estrus in pregnant cows compared to non-pregnant cows

DiscussionThe current results indicate the positive impact of treatment with anti-parasites (Ivermectin) onoccurrence rate of mastitis in Baladi cows. Mavrogianni et al. (2012); Mavrogianni et al. (2014) foundthat increased frequency of clinical or subclinical mastitis through the �rst two weeks post-partum inewes that suffer from indo-parasitic infections. Staphylococcus aureus is considered one of the majorpathogenic agents of the udder that causes mainly subclinical infection (mastitis) (Tenhagen et al. 2001;Leitner et al., 2003; Olde Riekerink et al., 2008). Infections by endo-parasites lead to decreasing weightgain, reduced nitrogen balance, negative affect metabolism of protein metabolism and suppressingimmune response in calves )Randall and Gibbs 1981; Wiggin and Gibbs, 1990). Ashraf et al. (2018)showed that cows which treatment with Ivermectin exhibited anti- Staphylococcus aureus activity thanother cows. Uhlir (1991) observed that antibody activity is increased after treatment with Ivermectin inrabbits. Backes (2016) reported that white blood cells and lymphocytes were greater in cows treated withanti-parasitic than control cows’ group. Similar results reported by Sajid et al. (2006); Ghassan et al.(2011); Jameel et al. (2015) who stated that treatment the cows with Ivermectin lead to increase totalnumber of white blood cells and lymphocyte cells in those cows and the re�ection of this on the raisingof the immunity in animals. Torres et al. (2016) observed that Ivermectin drug was effective againstbio�lm formation by Staphylococcus aureus. Recently, Heidary and Gharebaghi (2020) discovered manyeffects of Ivermectin drug to against some diseases and highly effective against many microorganisms itworked as (antimicrobial, antiviral, and anti-cancer) it called the wonder drug. Mastrangelo et al. (2012)reported that Ivermectin acts as an anti-viral agent versus to �avivirus by inhibiting its replication activity.Another recent studies by Lv et al. (2018); Yamasmith et al. (2018) underlined Ivermectin role effectivepotential as an antiviral able to reducing viral load in the host. Furthermore, Lim et al. (2013); Omansen etal. (2015) suggested that Ivermectin acts an anti-mycobacterial activity against Mycobacteriumtuberculosis and Mycobacterium ulcerans. In the light previous studies lower percentage of mastitis intreated cows group than untreated in the present study may be attributed to the effect of Ivermectin as ananti- antimicrobial (anti- Staphylococcus aureus) activity in cows udders.

Treatment with anti-parasites (Ivermectin) led to an improvement in the reproductive e�ciencymeasurements in cows, through a decrease in the period from birth until conception, as well as a higherpregnancy rate from the �rst service. The present �ndings correspond with that reported by Walsh et al.(1995); Sanchez et al. (2002) who found that the interval from calving to conception was less in dairy

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cows which treated with anti-parasites (Ivermectin or Eprinomectin) compared to untreated cows.Orellana et al. (1999) stated that treatment of cows with anti-parasite led to reduce the interval fromcalving to conception. Seliem et al. (2010) showed that infected buffaloes with internal parasites liverworm (Fasciola) need a long time from calving to conception (156.75, day) compared to non-infectedgroup (112.46, day). Mejía et al. (1999) stated that treatment the dairy heifers with anti-parasitic(Ivermectin) caused to increased growth rate and earlier onset of ovarian functions. Ballweber et al.(1997) suggested that used anti-parasites (Doramectin or Ivermectin) in cattle led to signi�cant increasein weight in drug-treated groups relative to untreated groups, ranging from 0.132 to 0.272 kg averagedaily gain. Lacau-Mengidoet al. (2000) observed that Ivermectin treated dairy heifers recorded increasedserum IGF-1, this cause to acceleration of sexual and somatic maturation. Buffaloes having poor bodycondition score had less number of small and large follicles in their ovaries hence low incidence of goodquality oocytes (Ahmed et al., 1999). Observed in ewes having poor body condition lowering LH secretionor decline its pulse frequency. This effect is mediated through glucose level, or insulin growth factor-I(IGF-1) (Snyder et al., 1999). De�ciency of energy is conceder one of most agents detrimental to reproductionof livestock (Dunn and Moss, 1992). McClure (1994) reported that energy de�ciency causing to inhibitovarian function at pituitary synthesis/release of gonadotropin. Level of IGF-1 is very important toovarian follicular development (Robinson, 1996). Backes (2016) who found that treatment with Long-Acting Eprinomectin (anti-parasites) lead to increasing conception rates compared to control group (89vs. 50%). Higher pregnancy rate (94%) for the beef cows that treated with anti-parasitic drugs comparedwith untreated beef cows 82% (Stromberg et al., 1997). Larson et al. (1995) suggested that pregnancyrate was higher (56.4%) in beef heifers that treated with Ivermectin than control heifers (25.6%).Pregnancy rate was 72% and 87% in control cows’ group and Ivermectin treatments group, respectively inOntario cow (Kaleyet al., 2019). Loyacano et al. (2002) stated that pregnancy rate was higher (78%) inbeef heifers that treatment with Ivermectin than no treatment heifers (54%). Volk et al. (2019) suggestedthat beef heifers which treated with Eprinomectin (anti-parasites) recorded greater (84%) pregnancy ratecompared with control group heifers (68%). Orellana et al. (1999) reported that treatment with anti-parasites was associated with increasing the conception rate. Seliem et al. (2010) showed that higherpregnancy rate in buffaloes that treated with anti-Fasciola drugs (67.7%) than control group buffaloes(16.7%). Hammam et al. (2011) found that the pregnancy rate in the healthy treated buffaloes was higher(55.6 %) than buffaloes’ infection with liver worm (Fasciola hepatica) (30.8 %). Hawkins (1993); Gross etal. (1999) stated that anthelmintic-treated beef cows recorded higher conception rate and calving ratecompared to untreated controls. The present results indicate increase the conception rate in treated cowsby anti-parasites compared to untreated cows may be due to improved weight gains and general bodycondition score of treated cows during postpartum period than untreated cows. Larson et al. (1995)reported that treatment beef heifers with Ivermectin improved weight gains and pregnancy rate during a60-dbreeding season. Barakat et al. (1995) showed that acute infection with nematodes worms (internalparasites) was associated with low incidences of conception rate and ovarian activity in cows andbuffaloes. Somchez et al. (2002) stated that removing external and internal parasites around calvingimprove the energy balance through the postpartum period and therefore improve the reproductiveperformance of cows. Maintaining of body weight and body condition score during postpartum period

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lead to increased energy balance and have also positive effect on reproductive performance of beef cows(Hess et al., 2005). Improving of body weight and body condition score of beef heifers which treated withextended-release Eprinomectin (anti-parasites) during breeding season may be the main cause toimproved their reproductive performance (Volk et al., 2019). Marked improvement was showed inreproductive performance of cow and heifers after administration of anthelmintic treatment compared tountreated controls (Andresen et al., 2017). Rehbein et al. (2013) reported that treatment with dewormingdrugs led to reduce worm burdens and increase weight gains in cattle. Infections with trematode (internalparasite) it causing depressed appetite and feed intake in affected sheep hence decreased availableenergy (Taylor et al., 2007; Rojo-Vázquez et al., 2012). El-Khadrawy et al. (2008) reported that buffalo-cows with (internal parasites) (Fasciola) recorded lower concentrations of serum Zn, Cu, Fe and Secompared to healthy animals. Ahmed et al. (1998) stated that buffaloes which have lowering in Cu or Znin blood are suffering to weak growth and infertility.

Cows treated with anti-parasites (Ivermectin) showed a decrease in ovarian dysfunction such asanestrous cases during the two months after parturition, which re�ected on the decrease in the periodfrom birth to conception in the treated cows. The current result is agreeing with that recorded by Barakatet al. (2001) who found that cows infected by internal parasites (liver worm) was associated with loss ofbody condition, decreased fertility and prolonged anoestrus period. Ahmed (2006); Ahmed et al. (2006)observed that infected buffaloes with internal parasites liver worm (Fasciola) recorded prolongedanestrous period compared with healthy animals. Stewart et al. (1992) stated that treatment of beefreplacement heifers with Ivermectin led to improved weight gain, feed e�ciency, and estrous activity.Barakat et al. (1995) showed that acute infection with nematodes worms (internal parasites) wasassociated with low occurring of ovarian activity in cows and buffaloes. Anthelmintic treated dairy cattlerecorded less time to recovering estrous during postpartum period (Sanyal et al., 1992). Liver �ukeinfections (Fasciolosis) in bovine were associated with ovarian inactivity and other infertility problems(Ahmed, 2007). Simsek et al. (2007) reported that 58% of repeat breeder cows were suffering from liverworm (Fasciola. hepatica). Jeffcoate et al. (1988); Fernandez-Abella et al. (2006) found that reduction inovulation rate and ovarian activity in infected ewes with internal parasites. El-Khadrawy et al. (2008)reported that lower concentrations of serum Zn, Cu, Fe and Se in buffalo which infected by liver worm(Fasciola)compared to healthy animals. Kommisrud (2005) suggested that there is a positive correlationbetween increased pre-partum blood selenium levels and decreased incidence of ovarian cysts andanestrus/silent estrus during the post-partum period in Norwegian dairy herds.

Cows treated with anti-parasites (Ivermectin) showed an increase in the levels of progesterone andestradiol at estrus, which had a positive impact on the high pregnancy rate from the �rst service. Thepresent result is agreeing with that reported by Waldman et al. (2001) who reported that a strong inverseassociation between the probability of non-return to estrus and progesterone concentration at the time ofestrus in cows. Busch et al. (2008) showed that pregnant cows have higher progesterone concentration atday 10 post- service compared with non-pregnant cow. The current result in agreement with that stated byLemley et al. (2010) found that increase of progesterone post- service was associated with elevatedpregnancy maintenance and improvement development of embryonic. Rivera et al. (2011) decrease

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progesterone concentrations during follicle growth in dairy cows lead to low cow embryo qualityproduction. Higher pre- and post- service progesterone concentrations were associated with improvementof the fertility. Progesterone modi�es ovarian and uterine function through direct effects or indirecteffects on fertilization and early stages from development of embryo (Cerri et al., 2011). El-Khadrawy etal. (2008) suggested that buffaloes have (internal parasites) (Fasciola) recorded lower concentrations ofblood Zn, Cu, Fe and Se compared to healthy animals. Kamada, (2017); Kassab et al. (2020) reported thatsupplementation of selenium to diet in dairy and beef cows led to increasing in progesterone andestradiol concentrations during estrous cycle. Sadek and Shaheen (2015) showed that there is increasingin serum progesterone in Baladi cows during postpartum after treatment with Ivermectin (anti-parasites)for up to 3 months. Opposite trend showed for estradiol in blood serum and returned to the increasingduring three months after treatment. Seliem et al. (2010) observed that increasing in progesterone anddecreasing in estradiol in blood serum of buffaloes that treated with (Anti-Fasciola-hepatica). Hammamet al. (2011) showed that infected buffaloes with liver worm (Fasciola) had a decrease in estradiolconcentrations (28.42 + 8.64 pg/ml) than the healthy group (39.61 + 18.23 pg/ml). Lopez-Diaz et al.(1998) found that Friesian heifers infected with liver �ukes (liver worm) recorded decline levels ofprogesterone than healthy animals. They suggested that liver �ukes may be able to alter normalmetabolism and/or balance of sex hormones. In conclusion, the current study indicated there is anassociation between treated cows with anti-parasites (Ivermectin) two months prepartum and incidencerate of mastitis beside an improvement in the reproductive performance in treated cows compared tountreated cows, therefore the present study recommends the herdsmen's treat their cows duringprepartum period by anti-parasites (Ivermectin) for less mastitis and improved reproductive performance.

DeclarationsData availability

The datasets generated during and/or analyzed during the current study are available from thecorresponding author on reasonable request.

Code availability

Not applicable.

Funding

Not applicable.

Ethical approval

The manuscript does not contain clinical studies or patient data.

Consent to participate

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Not applicable

Consent for publication

Not applicable.

Con�ict of interest

The author declares no competing interests.

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TablesTable 1: Speci�cations (Mean ± SE) of Baladi cow starting of treatment and at calving

Status of cow Untreated cows Treated cows

No. of cows 12 12

Body weight (kg) at starting of treatment  305.5± 6.5a 315.7± 9.4a

Body weight (kg) at calving 310.3±5.4a 370.6± 15.6b

Age (year) 8.5± 1.2 7.4± 1.1

Parity  3-5 3-5

BCS at calving 3 ≥3

a, b: values within the same row having different superscripts are signi�cantly different at (P <0.05)

Table (2). Speci�cations of IVOMEC® Plus drug (Ivermectin + clorsulon) adapted to US FDA (Food andDrug Administration) 2015

IndicationsDosage FormDrug TypeDrug

control of internal/external parasites incows

Subcutaneous Anti-parasitic

Ivermectin +clorsulon

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Table 3. Effect of treatment with anti-parasites on the time from calving to conceived (DO) days in Baladicows  

Items  Treated cows Untreated cows

Total no. of cows

The time from calving to conceived (DO) days:

X±SE 

12

 

86.5± 11.4a

12

 

123.3± 13.2b

a, b: values within the same row having different superscripts are signi�cantly different at (P <0.05)

 

Table 4. Concentrations of progesterone and Estradiol-17β at estrus, 7- and 21-day post-service in treatedand untreated Baladi cows

Hormones Treated cows  Untreated cows

Pregnant Non-pregnant Pregnant Non-pregnant

Progesterone (ng/ml):    

At estrus 0.37±0.09a 0.24±0.04b 0.25±0.02a 0.17±0.04b

7-day post- service 3.30±0.03a 2.10±0.01b 2.80±0.02a 1.90±0.03b

21-day post- service 7.21±0.12a 0.30±0.01b 5.13±0.12a 0.26±0.01b

Estradiol-17β (pg/ml):    

At estrus 37.30±0.32a 13.60±0.22b 22.10±0.11a 12.30±0.31b

a, b: values within the same row having different superscripts are different at (P <0.05). 

Figures

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Figure 1

See image above for �gure legend.

Figure 2

See image above for �gure legend.

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Figure 3

See image above for �gure legend.