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Efficacy of Ivermek OR against the poultry red mite

I.A. Arkhipov, Doctor of Veterinary Sciences, Deputy Director of the All-Russian Scientific Research Institute of Helminthology named after K.I. Skryabin V.E. Abramov, Doctor of Veterinary Sciences, Professor at the All-Russian Scientific Research Institute of Fundamental and Applied Parasitology of Animals and Plants named after K.I. Skryabin N.I. Koshevarov, Doctor of Veterinary Sciences, Senior Researcher at the International Scientific Research Center for Protection of Human, Animal and Environmental Health (LLC) V.I. Kidyaev, Candidate of Veterinary Sciences, ZAO AgroAtyashevo (AgroAtyashevo, CJSC), Republic of Mordovia (Russia) N.P. Biryukova, Candidate of Veterinary Sciences S.V. Rusakov, Candidate of Biological Sciences, All-Russian State Center for Quality and Standardization of Veterinary Medicinal Products and Feeds M.I. Safarova, Candidate of Chemical Sciences, Senior Researcher, Product Development Group, NITA-FARM

Introduction

Based on the results of conducted studies, it has been established that Ivermek OR for oral administration is highly effective and safe in controlling the poultry red mite. It is well tolerated by poultry at the therapeutic dose of 0.4 mg/kg based on ivermectin, and with prolonged daily use, it does not cause mortality or have a negative impact on the general condition and behavior of the birds.
Poultry farming is characterized by rapid reproduction rates, intensive growth, high productivity, and viability. One of the key factors in ensuring these advantages is the absence of ectoparasites in poultry houses.

Among the main parasites is the gamasid blood-sucking mite (Dermanyssus gallinae), commonly known as the poultry red mite. This parasite is widespread virtually everywhere and causes significant damage to poultry farming.

High mite infestation in chickens causes itching, restlessness, anemia, reduces live weight and egg production, and in cases of mass infestation can lead to mortality. In addition, mites are carriers of pathogens of borreliosis, ornithosis, fowl cholera, and Newcastle disease. Bites of the poultry red mite are also dangerous for humans – they can cause dermatitis and urticaria.

One of the methods for controlling mites in chickens is the use of broad-spectrum antiparasitic products.

Ivermek OR is a broad-spectrum antiparasitic product in a unique micellar water-dispersible form of ivermectin for oral administration, developed for effective control of the poultry red mite and other parasites.

The objective of this study was to evaluate tolerability, establish the therapeutic dose, and assess the antiparasitic efficacy of Ivermek OR against the poultry red mite.

MATERIALS AND METHODS

Initially, a clinical examination of chickens kept in cage housing was conducted at ZAO AgroAtyashevo (AgroAtyashevo, CJSC), Atyashevo district, Republic of Mordovia (Russia). In each poultry house, chickens were examined for the presence of mites, and groups were formed from the selected infested birds.

Chickens in the experimental and control groups were kept at an ambient air temperature of 21-28°C and relative humidity of 65-73%. The diagnosis of poultry red mite infestation was based on clinical signs, detection of arthropods on the birds' bodies, and in the housing environment. The average mite count (specimens per bird) was recorded. A light microscope MBS-9 was used to study mite morphology.
During clinical examination of birds in the experimental and control groups infested with Dermanyssus gallinae, the following signs were observed: pale mucous membranes, comb, and wattles; skin reddening; presence of papules; feather loss; feather pecking; and mite larvae on the body surface, most commonly under the wings. At the same time, the birds lost appetite, lost weight, and showed reduced egg production.
Ivermek OR was administered to birds in the experimental groups via drinking water. For this purpose, the calculated amount of the product was diluted in ¼ of the daily water consumption. To ensure guaranteed intake of the therapeutic dose, water supply was stopped 2 hours before administering the solution. The product was diluted on the day of use. Chickens in the control groups were left untreated.

Product efficacy against ectoparasites was evaluated 15 days post-treatment. During the trial, bird behavior and clinical condition were monitored, and the presence or absence of parasites on the body, along with the severity of clinical signs, were assessed.

The studies were conducted in spring 2013 in three stages by the All-Russian Scientific Research Institute of Helminthology named after K.I. Skryabin (Russia) and the International Scientific Research Center for Protection of Human, Animal and Environmental Health (Russia).

RESULTS AND DISCUSSION

At the first stage, product tolerability in young healthy birds was evaluated in two experiments. Given the oral route of administration, the therapeutic dose of the active ingredient was set at twice the injectable dose recommended in the instructions for Ivermek OR.

In the first experiment, the product was administered twice to 15 Ross-308 broilers, 19 days old, weighing 760-780 g. It was diluted in drinking water at a therapeutic dose of 0.4 mg/kg of active ingredient, with a 24-hour interval (birds had free access to medicated water). The control group (15 birds) received no treatment. Bird condition was monitored from the first administration until 10 days after the second dose.

Based on the results of the first experiment, the product did not have a significant effect on the general condition and behavior of the birds, except for two broilers that showed reduced activity for 1-2 days after administration. These symptoms were not observed in the following period. Water and feed intake, feather condition, activity, and response to external stimuli in the experimental group remained unchanged throughout the trial and did not differ from the control group. The body weight of chicks in both experimental and control groups was virtually identical both at the time of group formation and after completion of the experiment (Table 1). No mortality was recorded in the groups.

Table 1. Dynamics of chick body weight changes after administration of Ivermek OR (Experiment 1, n=15, P ≤ 0.05)

Group

Weight of chickens, g

0 day

1 day

5 day

10 day  

Experimental

772±11

832±12 

1109±19 

1469±19 

Control 

779±9  

843±13 

1117±18 

1483±22 

Table 2. Body weight gain in broilers after administration of Ivermek OR at different doses (Experiment 2, n = 10/20, P ≤ 0.05)

Study period, days

    Group     

 Group 1 (E)

  Group 2 (E)

Group 3 (E)

Group 4 (C)

Product dose, mg/kg of active ingredient

    0,4 

     1,2 

      2,0 

     –

     0

      965±27 

      947±30

     960±35  

     955±39

     1

      1012±26 

     968±34  

      996±38

     976±40

     5

     1294±34  

       1223±40   

     1272±45

     1224±35

     10

     1583±43   

     1499±42 

     1522±37

     1558±44

% of the initial body weight

     164,0 

     158,3  

     158,5

     163,1

Thus, the product was well tolerated even by poultry most sensitive to ivermectin and did not significantly affect the general condition and behavior.

In the second experiment, 70 Ross-308 broilers, 22 days old and weighing 930-990 g, were involved. They were divided into one control group (10 birds) and three experimental groups, with 20 birds in each. The product was administered to groups 1, 2, and 3 via an automatic watering system at the following doses:

  • Group 1 (E) – 0.4 mg/kg of body weight based on active ingredient (therapeutic dose)
  • Group 2 (E) – 1.2 mg/kg of body weight based on active ingredient (3 × therapeutic dose)
  • Group 3 (E) – 2.0 mg/kg of body weight based on active ingredient (5 × therapeutic dose)

During the first 10 days of the trial, body weight gain, feed and water intake were monitored, and biochemical and hematological parameters of the birds were controlled. Then, during the following 10 days, daily visual monitoring of bird behavior, motor activity, response to external stimuli, feed and water consumption, fecal characteristics, and flock survival was carried out.

Before administration of Ivermek OR, as well as 1, 5, and 10 days after the first administration, 3 chicks from each group were euthanized, and blood samples were collected to determine hematological and biochemical parameters using a Biosystems A-15 analyzer (Spain). The obtained results were statistically processed using the Student-Fisher method with t-test.
Based on the results of the second experiment, it was established that the product, administered for 7 days at therapeutic doses and at doses increased 3-fold and 5-fold, did not cause bird mortality and did not affect the general condition and behavior throughout the entire observation period (20 days).

Data on body weight gain dynamics in broilers after administration of the product at tested doses are shown in Table 2. They indicate that at therapeutic and elevated doses, the product does not affect body weight gain dynamics in broilers.
Table 3 presents hematological parameters in broilers over time after administration of Ivermek OR at therapeutic and elevated doses.

Table 3. Blood hematological parameters in broilers before and after administration of Ivermek OR at therapeutic and elevated doses (Experiment 2, n=3, P ≤ 0.05)

Time post-administration, days

Hemoglobin, g/%

Erythrocytes, 10¹²/L

Leukocytes, 10⁹/L

ESR, mm/h

Hematocrit, %

Platelets, ×10³/mm³

Leukocyte formula, %

Lymphocytes

Monocytes

Eosinophils 

Segmented neutrophils

 Dose: 0.4 mg/kg of active ingredient

     0

5,8±0,4 

3,3±0,4

5,2±0,7 

3±0   

29±2 

34±3

64±5  

5,2±0,7 

3,4±0,5 

28±3 

     1

6,1±0,3  

3,6±0,5

5,0±0,6 

3±0  

30±2

30±2

64±5 

5,5±0,9 

5,0±0,7 

25±4 

     5

5,5±0,3

3,7±0,5

5,3±0,8    

3±0

25±2   

33±4

70±6 

4,6±0,4 

4,0±0,5 

22±3 

     10

6,1±0,3

3,5±0,5

4,8±0,7   

3±0

32±2

34±4

65±6 

4,8±0,5 

4,3±0,6 

26±3 

   Dose: 1.2 mg/kg of active ingredient

     0

6,64±0,29

3,4±0,3 

5,2±0,6  

3±0

28±3

32±4

67±5 

4,4±0,5 

3,5±0,7 

25±3 

     1

6,81±0,40

3,5±0,4   

5,5±0,8

3±0

30±2 

33±3

68±6 

5,5±0,8 

4,0±0,6   

23±2 

     5

5,92±0,60

3,8±0,4 

5,3±0,7 

3±0 

29±3

30±3

65±6 

4,0±0,4 

4,0±0,5 

27±3 

     10

5,43±0,41      

3,5±0,3   

4,8±0,7

3±0

34±2

32±4

68±6 

4,2±0,4 

3,9±0,4 

24±4 

     Dose: 2.0 mg/kg of active ingredient

     0

5,82±0,36

3,4±0,5 

5,2±0,5

3±0

29±2 

30±4

67±6 

4,6±0,7 

4,1±0,8

25±35 

     1

6,90±0,50   

3,3±0,4

4,9±0,8

3±0

30±2 

32±4

64±6 

4,2±0,5 

4,0±0,5 

28±3 

     5

6,64±0,46   

3,4±0,5   

5,9±0,9

3±0

29±2 

30±4

83±7

4,0±0,4 

4,0±0,4 

9±2 

     10

6,20±0,30

3,6±0,5

5,0±1,0   

3±0 

30±2 

32±5

73±6 

4,2±0,5 

4,3±0,6 

20±3 

Control group

     0

6,10±0,37

3,7±0,5 

5,4±0,9

3±0 

31±3  

32±4

66±5 

4,5±0,4 

4,5±0,5 

25±3 

     1

6,70±0,52

3,3±0,5    

5,2±0,7  

3±0     

30±2 

31±3

68±6 

5,2±0,5  

4,1±0,5 

23±3 

     5

5,60±0,36   

3,8±0,5     

5,2±0,8    

3±0     

28±3 

32±3

72±6 

4,0±0,4 

4,1±0,4 

20±3 

     10

6,27±0,40   

3,3±0,4      

5,4±0,8   

3±0 

25±2 

31±4   

76±6 

4,3±0,5 

4,5±0,5  

21±3 

Key hematological parameters, such as hemoglobin level, erythrocyte, leukocyte, and thrombocyte counts, ESR, hematocrit, and leukocyte formula, showed no statistically significant changes compared to control birds.

Table 4 presents the results of biochemical parameter determination in broilers before and after administration of Ivermek OR.

Table 4. Blood biochemical parameters in broilers before and after administration of Ivermek OR at therapeutic and elevated doses (Experiment 2, n=3, P ≤ 0.05)

Group

Time post-administration, days

AST, U/L

ALT, U/L

Uric acid, μmol/L

Urea, mmol/L

Creatinine, μmol/L

Dose: 0.4 mg/kg of active ingredient

1      

     0

59±7

7,8±0,9 

436±42

0,8±0,2 

59±6 

     1

56±6 

12±1 

366±28 

0,8±0,1 

54±5 

     5

62±7 

8±1 

451±30   

0,6±0,1  

54±6 

     10

57±6  

8,2±0,9   

470±40   

0,5±0,1 

61±6 

Dose: 1.2 mg/kg of active ingredient

2 

     0

59±7 

6,5±0,8 

498±46 

0,4±0,1 

58±6 

     1

56±7 

16±2* 

590±34 

1,2±0,1*  

51±5 

     5

63±8 

6,9±0,9 

497±30 

0,7±0,1 

57±6 

     10

60±8    

6,5±0,8 

508±29 

0,7±0,1 

61±7 

Dose: 2.0 mg/kg of active ingredient

3

     0

57±6 

7±1 

529±45 

0,6±0,1 

50±6 

     1

59±8 

18±2* 

986±50* 

1,1±0,2* 

60±7 

     5

60±6 

10±1 

568±41 

0,6±0,1 

53±5 

     10

58±6 

9±1

480±30 

0,5±0,1 

63±7 

Control group

4  

     0

60±6   

8±1 

504±48 

0,6±0,1  

50±6 

     1

59±6 

7,5±0,8  

480±46  

0,6±0,1   

48±6 

     5

61±7 

6,6±0,8  

525±31   

0,6±0,1   

60±7 

     10

58±7   

9±1   

496±30   

0,7±0,1 

59±6 

* Differences are statistically significant compared to control.

As shown in the table, administration of Ivermek OR to birds at doses of 1.2 and 2.0 mg/kg body weight (based on active ingredient) resulted in a significant increase in alanine aminotransferase activity to 16±2 and 18±2 U/L, respectively, compared to the control value of 7.5±0.8 U/L on day 1 of the trial. A similar trend was observed at the therapeutic dose of 0.4 mg/kg of active ingredient, but the changes were not statistically significant.

Ivermek OR at a dose of 2.0 mg/kg of active ingredient caused an increase in uric acid and urea levels (to 986±50 μmol/L and 1.1±0.2 mmol/L, respectively, vs. 480±46 μmol/L and 0.6±0.1 mmol/L in control) 1 day after product administration. Uric acid and urea concentrations also increased at this time point in broilers receiving the product at 1.2 mg/kg of active ingredient.
On day 10 of the study, all blood biochemical parameters did not differ from baseline values or from the control group. No mortality was recorded through the end of the observation period (day 20), and all monitored parameters remained within physiological norms.

At the first stage, it was established that during evaluation of tolerability in young healthy poultry, administration of Ivermek OR at therapeutic doses and at doses increased 3-fold and 5-fold did not cause mortality or negative effects on the general condition and behavior of the birds.

At the second stage of the study, dose titration of Ivermek OR against Dermanyssus gallinae was conducted to refine the therapeutic dose. For this purpose, three experimental groups and one control group, with 10 birds in each, were formed based on the matching principle, all infested with the specified ectoparasite species. In total, 40 hens aged 7-8 months, kept in cages, were selected for the trials. The level of flock infestation with the poultry red mite prior to the trial is shown in Table 5.

Table 5. Trial design for evaluating Ivermek OR against Dermanyssus gallinae (n=10)

Group

Parasite count, specimens/bird

Product dose, mg/kg of active ingredient

Frequency

Re-administration 

Experimental groups

Group 1

16± 2 

     0,3

2

After 14 days

Group 2

16± 2 

     0,4

2

Group 3

15± 1

     0,5

2

Control group

Group 4

16± 2

–

–

–


As shown in the table, hens in experimental groups 1, 2, and 3 were infested with Dermanyssus gallinae at infestation intensities of 16±2, 16±2, and 15±1 specimens/bird, respectively. Birds in group 4, infested with Dermanyssus gallinae at 16±2 specimens/bird, served as the control.

Ivermek OR was administered to birds in different groups at three dose levels, twice with a 24-hour interval, and re-administered after 14 days. Birds in experimental groups 1, 2, and 3 received the product at doses of 0.3, 0.4, and 0.5 mg/kg, respectively. Birds in group 4 received no treatment and served as the control.

The results of the product trial at the second stage are presented in Table 6. They demonstrate its high efficacy against Dermanyssus gallinae at doses of 0.5, 0.4, and 0.3 mg/kg via drinking water, administered twice with a 24-hour interval and re-administered after 2 weeks.

Table 6. Efficacy of Ivermek OR at different doses against Dermanyssus gallinae

Group

Product dose, mg/kg and frequency

Parasite count, specimens/bird

Effectiveness, %

Before treatment

2 weeks after repeated treatment

Experimental groups

     1

     0,3×2

     16±2

     0,2

     98,7

     2

     0,4×2

     16±2 

     0

     100

     3

     0,5×2

     15±1

     0

     100

Control group

     4

     – 

     16±2

     17±2

     –

100% efficacy of Ivermek OR was achieved at doses of 0.5 and 0.4 mg/kg with three-time administration against the mites. In hens treated three times with the product at 0.3 mg/kg, single specimens of mite larvae were detected. The efficacy of Ivermek OR at this dose was 98.7%.

It should be noted that after treatment, the flock condition improved: clinical signs of the disease disappeared, and no mortality was recorded. The greatest effect was observed in birds after three-time administration of the product at doses of 0.4 and 0.5 mg/kg.

In hens of the control group, mite infestation intensified and the condition worsened: feather pecking, restlessness, feather loss, reduced appetite, and body weight loss were observed. The arthropod count increased and averaged 17±2 specimens/bird.

Thus, it was established that the best results were obtained with three-time administration of the product at doses of 0.4 and 0.5 mg/kg. The dose of 0.4 mg/kg via drinking water, administered twice with a 24-hour interval and re-administered after 14 days, was recommended as optimal for field trials of Ivermek OR.

At the third stage, field trials of the product were conducted at ZAO AgroAtyashevo (AgroAtyashevo, CJSC) on replacement pullets of the Hy-Line Brown cross (1,660 birds, 10-11 weeks of age). Dermanyssus gallinae mites were detected in 13.5% of the flock, with an infestation intensity of 16±1 specimens/bird. The diagnosis was based on clinical examination and detection of ectoparasite larvae on the birds' bodies, as well as mites in other habitats – litter, cracks, and crevices. Infested hens showed unkempt, dull plumage and reduced body weight. The infested flock was divided equally into experimental and control groups.

In the experimental group, the product was administered twice with a 24-hour interval at a therapeutic dose of 0.4 mg/kg body weight based on ivermectin; re-treatment was performed after 2 weeks. The control group received no treatment.

During the efficacy trial, product safety was also assessed based on the following parameters: bird behavior, motor activity, feed and water intake, feather condition, fecal characteristics, and analysis of morphological and biochemical blood parameters in hens (10 birds from each of the experimental and control groups).

The data obtained at the third stage under field conditions demonstrated the convenience of administering the product via drinking water, as well as its high efficacy against mites and good tolerability in poultry.

The therapeutic dose of 0.4 mg/kg based on active ingredient, administered three times via drinking water, achieved 97% efficacy.

Blood analysis results for hens in the experimental and control groups are shown in Table 7.

Table 7. Blood analysis results in hens (n = 10, P ≤ 0.05)

Parameters

Group

Experimental

Control 

Erythrocytes, 10¹²/L

2,8±0,8 

2,7±0,2 

Hemoglobin, g/L

93±2 

93±2

Total protein, g/%

4,5±0,4 

4,8±0,4 

Calcium, mg/%

21±3 

20±4 

Phosphorus, mg/%

7,2±0,7 

7,2±0,8 

AST, U/L

49,1±0,7 

42,4±0,6 

ALT, U/L

22,3±0,3 

21,7±0,3 

The obtained data indicate that the product at a therapeutic dose of 0.4 mg/kg based on active ingredient, administered three times via drinking water, does not have a negative effect on the physiological condition of poultry, including morphological and biochemical blood parameters, which do not differ from those of the main flock of replacement pullets.

CONCLUSION

The studies demonstrate that Ivermek OR for oral administration:

  • is highly effective and safe in controlling the poultry red mite

  • is well tolerated by poultry at a therapeutic dose of 0.4 mg/kg based on active ingredient, and with prolonged daily use does not cause mortality or affect the general condition and behavior of birds

  • is recommended for control of Dermanyssus gallinae at a therapeutic dose of 0.4 mg/kg based on active ingredient via drinking water, administered twice with a 24-hour interval and re-administered after 14 days.

REFERENCES

  1. Arkhipov I.A. Antihelminthics: pharmacology and application. Moscow: Publishing House of the Russian Academy of Agricultural Sciences, 2009. 405 p.
  2. Pomerantsev B.I. ixodid ticks (Ixodidae). Moscow; Leningrad: Publishing House of the Academy of Sciences of the USSR, 1950. 224 p. (Fauna of the USSR. Arachnids. Vol. 4, Issue 2).
  3. Serdyukova G.V. Ixodid ticks of the fauna of the USSR. Moscow; Leningrad: Publishing House of the Academy of Sciences of the USSR, 1956. 121 p.
  4. Koch F. Fliegenals Übertrager von Dermanyssus gallinae// Vet. Rec. 1964. V.4. P. 33-63.

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