Low Dose Doxycycline Treatment to Control Periodontal Disease in Multiple Primate Species—A Preliminary Report
American Association of Zoo Veterinarians Conference 2002

E.J. Bicknese1, DVM, MPVM; D.A. Fagan2, DDS

1San Diego Zoo, San Diego, CA, USA; 2The Colyer Institute, San Diego, CA, USA


As a result of the relative inability to obtain a satisfactory oral examination on a regular basis, and to perform routine dental treatments without anesthesia, chronic periodontal disease in non­human primate species has been difficult to treat, and almost impossible to resolve or prevent in most species. This presentation discusses a small clinical trial considering the long-term use of two convenient low dose doxycycline suspensions1 (raspberry-flavored suspension and raspberry/apple-flavored suspension), often used in a pulsatile manner, to control and in some cases, completely resolve chronic periodontal disease in several captive non-human primate species.

It is not uncommon to find periodontal infections in many primate species living in captive environments. Periodontal disease can be severe, chronic, generalized, and debilitating. Advanced oral disease is often accompanied with the potentially detrimental, systemic impact of chronic, intermittent, transient bacteremia. Prolonging the anesthesia in the patient with chronic oral infection is not always a safe alternative. Moreover, it is well known that the beneficial effects of routine oral prophylaxis are amazingly short lived at best, and often detrimentally contributes to the patient’s systemic bacteremia. This situation has not availed itself to resolution because until recently there has not been a convenient, available, clinical solution to address this severe oral problem.

In the past few years, as researchers have unlocked the secrets surrounding the cellular and molecular mechanisms of periodontitis, the role of the host’s (patient’s) immune system response in the initiation and progression of the disease process has become quite clear. As a result, host modulating pharmacotherapies as adjuncts to traditional antimicrobial therapy have become the standard of care for the clinical management of human periodontal infections. An understanding of these new strategies has presented the potential for effectively treating, and perhaps finally preventing the recurrence of periodontal disease in captive primate species. Routine dental scaling, gingival curettage, and root planning still needs to be done on a routine basis, when and where indicated, to remove accumulated plaque and calculus. Also, a therapeutic course of appropriate, broad spectrum antibiotics (for example3 clindamycin hydrochloride 5.5–125 mg/kg BID–TID, metronidazole benzoate 25 mg/kg BID, amoxicillin 20 mg/kg BID) in the advanced cases is always indicated to correct any overt purulent situations. When these two treatment modalities are used in combination, the result seems to be a long-term corrective treatment protocol, which offers very positive signs of success in preventing the recurrence of this all-too-common periodontal disease process.

The authors have safely and effectively utilized this long-term, low dose, doxycycline treatment protocol in 10 animals of seven species.3 There has been some variations in dosing as a result of the different management practices specific to the individual species, but generally 0.3 mg/kg PO BID × 90 days—stopped for 90 days—and the repeated for another 90 days—on and off again. In some animals, several treatment cycles caused complete resolution and the treatment cycles have stopped. Other animals, that had either very severe periodontal disease or are anesthetized infrequently to monitor recurrence, will be on the on/off cycles indefinitely. As a direct result of the small volume of drug necessary per dose, and the very pleasant flavor of the suspensions, dosing compliance has been very successful overall. This treatment protocol seems to be very well tolerated. It has also been used in a colobus monkey, a species often difficult to medicate due to its folivorous diet and sacculated stomach.

A very thorough discussion of how and why this treatment protocol works is available in the article “Modulation of the Host Response in the Treatment of Periodontitis” by Golub et al. listed in the reference list below. A copy of this article was provided at the presentation. Clearly, more clinical evaluation in numerous other species is necessary before this protocol becomes standard of care but considering the magnitude of the impact of chronic periodontitis on the captive primate population, early presentation of these limited results was considered essential. The authors are in the early stages of treating a few small carnivores with this protocol and are hopeful it will be effective in carnivore species also.

A small clinical trial of a widely used human treatment protocol to address chronic non-human primate periodontitis, with a modest modification in dosing has resulted in the proposed availability of an unusually safe, effective, and reasonably-priced treatment modality. This protocol has provided another urgently needed treatment option for the exotic animal veterinarian, which seems to improve the health and quality of life of various non-human primate charges.

Doxycycline Products1

Vibramycin® 5 mg/ml: raspberry flavored doxycycline monohydrate; good for 2 weeks after reconstitution; Pfizer labs, Division of Pfizer, Inc., NY, USA.

Vibramycin Calcium Syrup® 10 mg/ml: raspberry-apple doxycycline calcium suspension; extended shelf life; Pfizer labs, Division of Pfizer, Inc., NY, USA.

Dosages2

The dosages listed for clindamycin, amoxicillin, and metronidazole have not been determined by pharmacological studies but has been clinically effective and appear safe in many non-human primate species.

Due to their folivorous diet and sacculated stomachs, the clindamycin hydrochloride (Upjohn Company, Kalamazoo, MI, USA) has not been used in species like colobus or langurs. Metronidazole has been used frequently in colobus/langur species without adverse effects; amoxicillin has only been used cautiously and occasionally in colobus/langur species.

Species Successfully Treated3

  • Allen’s swamp guenon—one animal Cercopithecus nigroviridis
  • Bengal slow loris—four animals Nycticebus coucang bengalensis
  • Colobus monkey—one animal Colobus polykomas kikuyuensis
  • Crab-eating macaque—one animal Macaca fascicularis
  • Mainland drill—one animal Mandrillus leucophaeus
  • Golden-bellied mangabey—one animal Cercocebus galeritus
  • Sumatran orangutan—one animal Pongo pygmaeus abelii

References

1.  Caton JG, Ciancio SG, Blieden T, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planning in patients with adult periodontitis. J Periodontol. 2000;71:521–532.

2.  Crout RJ, Lee HM, Schroeder K, et al. The “cyclic” regimen of low-dose doxycycline for adult periodontitis: a preliminary study. J Periodontol. 1996;67:506–514.

3.  Golub LM, Sorsa T, Lee HM, et al. Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. J Clin Periodontol. 1995;22:100–109.

4.  Golub LM, Ryan ME, Williams RC. Modulation of the host response in the treatment of periodontitis. Dentistry Today. October 1998;17(10).

5.  Ingman T, Sorsa T, Suomalainen K, et al. Tetracycline inhibition and cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article. J Periodontal. 1993;64:82–88.

6.  Listgarten MA. The structure of dental plaque. Periodontal 2000. 1994;5:52–65.

7.  Sorsa T, Ding Y, Lauhio A, et al. Effects of tetracyclines on neutrophil, gingival, and salivary collagenases. A functional and western-blot assessment with special reference to their cellular sources in periodontal diseases. Ann NY Acad Sci. 1994;732:112–131.

8.  Sorsa T, Ding YL, Ongmam T, et al. Cellular source, activation, and inhibition of dental plaque collagenase. J Clin Periodontol. 1995;22:709–717.

9.  Vemillo AT, Ramamurthy NS, Golub LM, Rifkin BR. The nonantimicrobial properties of tetracycline for the treatment of periodontal disease. Curr Opin Periodontal. 1994;111–118.

10.  Walker C, Gordon J. The effect of Clindamycin hydrochloride on the microbiota associated with refractory periodontitis. J Periodontol. 1990;61:692–698.

11.  Walker CB, Pappas JD, Tyler KZ, Cohen S, Gordon JM. Antibiotic susceptibilities of periodontal bacteria. In vitro susceptibilities to eight antimicrobial agents. J Periodontal. 1985;56(Suppl):67–74.

12.  Walker CB. The acquisition of antibiotic resistance in the periodontal microflora. Periodontal 2000. 1996;10:79–88.

 

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

E.J. Bicknese, DVM, MPVM
San Diego Zoo
San Diego, CA, USA


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