Preliminary Studies on the Use of Oxytetracycline to Control Hatchling Alligator Syndrome (HAS)
IAAAM Archive
P.T. Cardeilhac; B.R. Collin; F. Ruisi; S. Sundloff; R. Larsen; T. Lane
Department of Special Clinical Sciences, Reproduction and Preventative Medicine, College of Veterinary Medicine, University of Florida, Gainesville, FL

Abstract

The most important infectious disease problem associated with alligator farming is the variety of bacterial diseases that occur in hatchlings before their immune system becomes fully competent. This complex of infections has been termed Hatchling Alligator Syndrome (HAS). HAS may be caused by primary infection but it usually results from subclinical infections with one or more opportunistic organisms. The infections primarily occur in animals made susceptible through stress induced by management practices. Clinical signs of HAS include poor condition, slow growth and death. Oxytetracycline has been found to be useful in the control of HAS. In this study estimation of an optimum dose for oxytetracycline was performed using 160 animals (4 groups of 40) and the optimum bracketed by the number of lagging animals and deaths in each group. An exact dose was calculated by plotting rate of gain vs. dose, using a quadratic model, and determining the maxima by derivatives. Growth rates were determined in inches/day x 1000 over a defined period of time. Condition was the cube root of weight/length x 1000 (3.fWt/L x 1000). The optimum dose (300mg/kg feed) was field tested using over 796 animals in 2 trials. In both trials the number of lagging animals was reduced following treatment with oxytetracycline.

Introduction

A complex of bacterial infections may attack hatchling alliga to rs (1,2). Most ot these infections occur before the alligators reach 2 feet in length - apparently after the depletion of passive immunity received from the yolk but before their intrinsic immune system becomes fully competent. This complex of infections has been termed Hatchling Alligator Syndrome (HAS). The infections are occasionally primary, but HAS usually results from subclinical infections by one or more opportunistic organisms. Infections often occur after stress induced by management practices. Clinical signs of HAS include lethargy, slow growth, poor condition and death. The farmer finds a reduced feed consumption and an increase in the number of animals considered to be lagging (animals which grow slowly and are in poor condition). Lagging animals caused by HAS are often in poor condition which differentiates them from well but slow growing animals.

Hatchling alligators usually must be treated as a group primarily because of the numbers involved. Many Florida Alligator farms raise 1000 or more hatchlings each year. Most of the farms give feed additives to the hatchlings in the form of a premix containing vitamins and minerals. Thus, a convenient treatment regimen was available, i.e., add antibiotic to the premix after determining the antibiotic susceptibility of the organisms involved. The aim of this study was to determine an optimum dose for oxytetracycline (OTC) and demonstrate safety and effectiveness of the treatment by clinical trials

Materials and Methods

Rate of gain in length was determined in inches per day x 1000 over a defined period of time (15 September to 15 December). Lagging animals under the conditions of this study were those with a rate of gain in length < 36. Coefficient of body condition is defined as the cube root of the weight divided by length x 1000 (3 Wt/L) x 1000. Organisms were isolated from animals suffering from HAS by culturing blood, lung, liver, kidney and any observed lesions. The susceptibility of isolates to selected anitbiotics and the disc potency (in mcg) was as follows: Tetracycline: (TM-30); Ampicillin, (SM-10); Chloramphenicol: (C-30); Erythromycin: (E-10); Gentamycin: (GM-10); Kanamycin: (K30); Polymyxin-B: (PB-300); Trimethoprim and Sulfamethoxazole: (SXT) 1.25 + 23.75); Vancomycin: (VA-30). Oxytetracycline Premix (Terramycin D-50) was furnished by Pfizer Inc. (Lee's Summit, MO). Oxytetracycline content of the premix was determined at the beginning and termination of the experiment and the determined concentration differed by less than 15% from the calculated concentration. Estimation of a optimal dose was performed using 4 groups of animals. Each group contained 40 animals kept in 2 pens with 20 animals per pen. Dose of OTC given to each group was 0, 75, 225, or 450 mg per kg of feed. The animals were treated continuously for 161 days and data evaluated based on growth lagging animals and deaths. An optimal dose was approximated by the numbers of deaths and lagging animals in the group. The exact dose was calculated by regression analysis of gain in weight and length over treatment periods of 42, and 84 days. Derivatives were used to determine the maximum performance verses dose levelfor a quadratic model. Clinical trials were then performed using the determined optimum dose.

Results

Susceptibility of Organisms Causing HAS to OTC

Fifty (50) organisms were isolated from animals suffering from HAS. The organisms were taken from the following tissues (number of isolates): skin (10); blood (8); eye (1); lung (11); liver (3); kidney (10); Pharynx (1); tonsil (4). Twenty three (23) % of the organisms tested were susceptible to tetracyclines (disc potency = 30mcg).

Dose Titration

Gain in length, condition, number of lagging animals and deaths for 84 days of treatment with 0, 75, 225, and 450 mg OTC per kg of feed indicate an optimum dose between 225 and 450 (Table 1).

Table 1: Treatment of Hatchling Alligators with OTC in Florida to Control HAS

 

Performance (Day 84)

Group (%)
(n = 40)

OTC (2)

Gain Rate (3,4)

Condition (3,5)

Lagging(%)(6)

Deaths (%)

Untreated

0

23 (8)

363 (12)

30 (75)

5 (13)

OTC 75

75

36 (14)

366 (18)

18 (45)

0 (0)

OTC 225

225

48 (12)

374 (13)

5 (13)

0 (0)

OTC 450

450

43 (12)

381 (46)

7 (18)

0 (0)

1.  Eighty-four day study period using hatchlings < 14 days of age 20 Sept 83 to 13 Dec 83.

2.  mg/kg feed.

3.  Value is mean and (standard deviation.

4.  Rate in inches/day x 1000.

5.  Condition = (cube root of Wt/L) x 1000. Value is mean and (standard deviation).

6.  Lagging animals were identified by 1984 criteria, i.e. daily growth ratio in (inches) x 1000 of <36.

Analysis of variance showed that there were groups by day of treatment interactions for both length and weight; therefore optimum dose was calculated after 42 and 84 days of treatment for gain in length and weight. Four values for optimum dose were obtained (302, 300, 308, 290) with a mean value of 300 (S.D. = 7.5). Optimum dose was considered to be 300 mg OTC per kg of feed.

Clinical Trials

Satisfactory clinical trials using the calculated optimum dose (300mg OTC/kg feed) have been performed on 2 farms in different states (Louisiana, and Florida). One trial was conducted at a farm in Kissimmee Florida. The performance of 284 hatchlings treated in 1984 was compared with 312 hatchlings which had not been treated in 1983. The trial ran for approximately 90 days (86 and 90 days respectively) from approximately 15 September to 15 December each year. The results are summarized in: mean length at day 0, treated = 10.6 (S.D. 0.3), controls = 10.8 (S.D. 0.3); Condition at day 0, treated 363 (S.D. 7.4), controls 360 (S.D. 6.6); length at day 90, treated = 15.5 (S.D. 0.4), controls 13.5 (S.D. 0.4); condition at day 90, treated = 387 (S.D. 7), controls = 362 (S.D. 11); mean gain in length day 90, treated = 5.6 (S.D. 1), controls = 2.7 (S.D 0.4); mean rate of gain in length, treated = 65 (S.D. 12), controls = 29 (S.D. 4); lagging animals treated 6 (2%), controls = 224 (72%) (Table 2).

Table 2: Treatment of Hatchling Alligators with OTC in Florida to Control HAS (1)

 

Day 0

Day 90

Performance

Group

N

Length (2)

Condition (2,3)

Length (2)

Condition (2,3)

Gain (2)

Rate (2,4)

Lagging (%)(5)

Deaths

Control 1983

312

10.8 (0.3)

360 (6.6)

13.5 (0.4)

362 (11)

2.7 (0.4)

29 (4)

224 (72)

0

OTC

284

10.6 (0.3)

363 (7.4)

15.5 (0.4)

387 (7)

5.6 (1)

65 (12)

6 (2)

0

1.  OTC given at 300 mg/kg feed for 86 days (18 Sept 84 to 14 Dec 84). Control group cultured for 94 days (9 Sept 83 to 13 Dec 83).

2.  Mean and (standard deviation).

3.  Condition = (cube root of wt/L) x 1000.

4.  Rate = gain/day in inches x 1000.

5.  Lagging animals grew at a rate of <36.

A second trial was conducted at a farm near Lake Charles, Louisiana (Table 3). The treatment period was 56 days from 4 September until 29 October 1985. One hundred (100) hatchlings were given OTC at 300mq/kq feed (ground whole nutria fortified with a vitamin/mineral additive). A control group of 100 hatchlings received only the feed. Performance over the period is as follows: mean length day 0, treated = 10.5 (S.D. 0.5), controls = 10.1 (S.D. 0.4); mean length day 56, treated = 15.4 (S.D. 1.1), controls = 12.9. (S.D. 10.8); gain in length, treated 4.8 (S.D. 1.1), controls 2.4 (S.D. 1.1); mean rate of gain in length, treated = 86 (S.D. 20), controls = 43 (S.D. 20); mean condition day 0, treated 358, controls = 367; mean condition day 56, treated = 372, controls 380; lagging animals, treated = 1 (1%), controls = 4 (4%).

Table 3: Clinical Trial in Louisiana to Control HAS in Hatchling Alligators (1)

 

Day 0

Day 56

Performance

Group

N

Length (2)

Condition (3)

Length (2)

Condition (3)

Gain (2.4)

Rate (2,4)

Lagging (%)(5)

Deaths

Control

100

10.1 (0.4)

367

12.9 (0.8)

380

2.4 (1.1)

43 (20)

4

0

Treated

100

10.5 (0.5)

358

15.4 (l.1)

372

4.8 (1.1)

86 (20)

1

0

1.  OTC given at 300 mg/kg feed in treated group for 56 days (4 Sept 85 to 29 Oct. 85).

2.  Values given are mean and (standard deviation).

3.  Condition = (cube root of wt/L) x 1000.

4.  Growth in inches/day x 1000.

5.  Lagging animals are those that grow at a rate <36.

Animal Safety

A group of 40 animals were treated with 1.5 x the optimal dose of OTC (450 mg OTC/kg feed) for a period of 40 days. The 1.5x treated group was not significantly different from a control group which received feed without OTC, and an I.Ox (300 mg OTC/kg feed) group. The groups were compared for gain in length, condition, numbers of lagging animals, clinical values (total protein, albumin, globulin, SGOT, SGPT, alkaline phosphatase, Na, K, Cl, C02, Ca, P, erythrocyte count, packed cell volume, leucocyte count) and organ weights (lungs, kidneys, liver, percentage of body weight represented by each organ).

Discussion

The present study offers experimental evidence to support the practice of controlling HAS by treatment with OTC. An optimal dose was approximated by observing the number of lagging animals, deaths and performances in groups treated with different levels of antibiotic. In order to find an exact dose the effect of different levels of antibiotic on rate of gain in length and weight was determined. This seemed to be the best way to estimate an optimum dose of OTC used to treat a complex disease whose principle clinical sign is lagging animals. Confirmation of efficacy for this determined dose was accomplished by clinical trials with treatment of animals being cultured for commercial purposes. Continuous feeding of 1.5x the determined optimal dose for 42 days indicates that substantial error (50% overdose) in dose calculation can be tolerated for an extended period of time without apparent harmful effects.

OTC has been found to be a useful and safe drug for many areas of animal production. The use of this antibiotic in an approved manner will be of value to alligator production but it will not control all bacterial infections. Preliminary results in our laboratory indicate a number of organisms associated with HAS are resistant to OTC.

Other causative organisms may become resistant to OTC. HAS can be devastating to a culture unit with losses exceeding 90% of the hatchling crop (1). isolation of the agent from blood or lesions and determining susceptibility to OTC should accompany treatment.

References

1.  Lane, T.J., Boyce, W.M., Rinehard, M.K., Larsen, R.E., Poulos, P.W. King, M.M., Burgelt, C.D., Cardeilhac, P.T., Disease Problems in Farm-Raised Hatchling Alligators on Florida Alligator Farms. IAAAM Proceedings, 1:9-12 (1984).

2.  Shotts, E.B.Jr., Bacterial Diseases of Alligators: An overview. In: Proceedings First Annual Alligator Production Conference, P.T. Cardeilhac, T. Lane and R. Larsen, Eds. IFAS University of Florida 1981, pp36-41.

Speaker Information
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Paul T. Cardeilhac, DVM, PhD
University of Florida, College of Veterinary Medicine
Gainesville, FL


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