Babesia

HISTORY:

First described in the late 1800’s across South Africa, this protozoal disease was first thought to be canine distemper in “billary form”. In North America the first report of Babesiosis was made in 1934, and was presumed to belong to the large Babesia spp. B. canis vogeli. The first endemic case of a small piroplasm reported to infect a North American canine was in 1968; the canine was imported from Kuala Lumpur, also an endemic area of the world.

Since the mid 90’s North America has had a significant rise of cases of Babesiosis, with a study completed in 2003 showing the geographic distribution across the entire United States, and 1 Province in Canada. Dogs positive for Babesia DNA were located in 29 states and 1 province (Ontario). B gibsoni (Asia) was the most commonly detected species, with B gibsoni (Asia) detected in samples from 131 of 144 dogs. Of 131 dogs positive for B gibsoni (Asia), 122 were American Pit Bull Terrier’s. Of the 10 dogs positive for Babesia canis vogeli, 6 were Greyhounds. In the dogs that were not American Pit Bull Terrier’s, there was a history of recently being bitten by another dog, particularly an APBT.


OVERVIEW/CLASSIFICATION:

Babesiosis is a disease caused by a protozoan parasite belonging to the genus Babesia. The stage infecting mammalian RBC’s include merozoites, also named piroplasms. They infect and replicate inside RBC’s resulting in both direct and immune-mediated hemolytic anemia (IMHA). IMHA is more clinically important then direct hemolytic anemia caused by piroplasm, as the degree of signs is not directly dependent on the level of parasitemia.

Currently there are 4 large Babesia spp. known to infect canines. Large piroplasms (4-7 um) and geographic distribution include B. canis vogeli - United States, Canada, Africa, Asia, Australia. B canis rossi – Africa (most pestiferousness subspecies), B. canis canis – Europe, Asia and lastly an unnamed North Carolina Isolate spp.

Currently there are 3 known small Babesia spp. known to infect canines. Small piroplasms (2-5 um) and geographic distribution include B. gibsoni – worldwide, emerging problem in United States and Canada, B. conradea – California, Western United States (formerly B. gibsoni California), and a Babesia microti-like piroplasm (named Theileria annae) – Spain, Europe.




SIGNALMENT/CAUSES & RISK FACTORS:

Risk factors include recent tick attachment; R. sanguineus the vector for B. canis is very common in the United States. Haemaphysalis spp., the vector for B. gibsoni, has yet to be identified in the United States. R. sanguineus is often referenced as a competent vector for B. gibsoni, but no studies have been preformed, and canine bites remain the highest risk for transmission. Tick transmission of babesia requires 2-3 days of tick-host feeding contact, with a prepatent period of 7-28 days.

Breeds such as the American Pit Bull Terrier, American Staffordshire Terrier, and Greyhounds are more likely to test positive for babesiosis in North America, but any breed may acquire the disease. About 50% of APBT surveyed tested positive using PCR testing methods for B. gibsoni in one study. A study conducted in Victoria, Australia; 17.5% APBT/Staffordshire tested were positive for B. gibsoni. Any breed of canine can be infected in Asia, Europe and Africa.

Recent blood transfusion puts a canine at risk for infection, and has been associated with infections. As some donors are Greyhounds, it is suggested that all blood donors in endemic areas have a spleen biopsy sent for PCR testing for Babesia spp. DNA.

Kennels seem to have a higher percentage of infection; Greyhound kennels have a higher prevalence of B. canis then pet greyhounds. American Pit Bull Terrier kennels have a higher prevalence of B. gibsoni. A kennel with a positive B. gibsoni dog usually will have a high infection rate of 10-50%.

Use of needles and syringes, which include direct sharing, improper sterilization techniques of syringes or needles have also been reported as sources of infection. Kennels with large numbers sometimes will vaccinate multiple puppies with 1 needle and syringe, or treat multiple infections with improperly sterilized equipment.

Breeding and transplacental transmission has been studied in a controlled situation, and proven to happen, with pups 10 days and younger testing positive, in shorter time then the prepatent period for tick transmission.

Splenectomized and immune suppressed canines may show more severe signs and increased parasitemia.


SYSTEMS AFFECTED/CLINICAL SIGNS:

Hemic, lymphatic, renal, hepatic and immune systems are affected. Signs include anorexia, lethargy, weight loss, pale mucus membranes, anemia (mild to severe), fever, thrombocytopenia (bleeding tendency is rare), icterus, splenomegaly, hepatomegaly, pigmenturia and lymphadenopathy. Renal/urological effects result in renal failure and metabolic acidosis. GI signs include vomiting, diarrhea and dark/orange feces from increased bilirubin excretion. Cerebral babesiosis (B. canis rosi) signs include weakness, disorientation, and collapse.
Signs seem to vary depending if disease is latent, chronic or active, and also depending on Babesia spp. involved. Other factors include age, stress/activity and immune status, and presence/absence of the spleen.


LABORATORY DIAGNOSTIC TESTING:

Differential diagnosis should include any disease involving immune-mediated hemolytic anemia such as, ITP, Heamobartonellosis, Ehrlichiosis, Rocky Mountain spotted fever and systemic lupus erythematosus. Diseases involving non-immune mediated hemolytic anemia including splenic torsion, zinc toxicity, Heinz body anemia, DIC, PK and/or PFK deficiency and heartworm caval syndrome. Problems associated with hepatic and posthepatic jaundice should also be examined, including rupture or obstruction of biliary and Leptospirosis.

Laboratory tests that should be preformed include a Full Complete CBC, biochemistry and urinalysis. Findings can vary depending on acute, chronic or latent infections; with most chronic or latent carriers there will be very little signs beyond a positive PCR test. Blood cells found to be in high ranges include reticulocytes (if regenerative anemia), WBC and neutrophils (variable, leukopenia has been reported). Blood cells found to be in low ranges include lymphocytes, eosinophils, total RBC’s, hemoglobin, MCV, PCV and platelets. Blood chemistries found to be in high ranges include BUN, creatinine, direct and total bilirubin, AST, ALT, GGT, globulin (variable, reported low as well) and total protein. Low blood chemistries include albumin.

Diagnostic testing includes microscopy, serology and polymerase chain reaction (PCR). Microscopy involves using in house quick stains, always use capillary blood, and scan the feathered edge as large piroplasms migrate to that area on slide. Microscopy is best preformed when looking for large piroplasms, or with acute cases, not good for diagnosing genotype, species or sub species, and can also result in false negatives or positives. Serology or immunofluorescent antibody (IFA) is common and available in most areas. True sensitivity is not known, and also not useful for diagnosing genotype, species or sub-species. Another test that can be preformed is a combs test, co-infection with erilichia, baronella, mycoplasma, leishmania and/or rickettsia have been identified and dogs with babesia will often test positive, making it a necessity to perform other tests to distinguish between other causes of anemia. PCR testing to this point is the most reliable and cost effective method of diagnosing babesiosis, amplifying small fragments of the Babesia spp. DNA. Available at most laboratories, although not all PCR tests are the same. While false negatives are possible, and false positives are rare, it is a very sensitive test with one test detecting DNA 87% of the time and going up to 100% when two test are preformed 2-4 weeks apart.

 

MANAGEMENT/THERAPEUTICS & FOLLOW UP

Experts suggest that since the prevalence of babesia has increased, that specific anti-babesial treatment is indicated and proper in dogs highly suspected of having babesia, even without definite diagnosis. In regards to treating B. Gibsoni, the research continues, with the combination of Atovaquone and Azithromycin showing the best efficacy. Other combination antibiotic treatments have been employed with little success, while combinations of anti-protozoal and antibiotics have not had much success either.

Antibiotics do not cure babesiosis, but they are however a reasonable choice of treatment while awaiting diagnosis, and proper anti-babesial medication. Three antibiotics are the most commonly used in these cases, Doxycycline, Clindamycin and Metronidazole. Doxycycline is the antibiotic of choice for most doctors, dosages of 10mg/kg PO, BID or IV, SID for 7-10 days will decrease clinical signs, morbidity and mortality. Clindamycin dosed at 12.5-25mg/kg PO, BID for 7-10 days has been shown to do a good job and decrease clinical signs, morbidity and mortality. Metronidazole dosage of 25-50mg/kg PO, BID for 7 days has also been shown to decrease clinical signs, morbidity and mortality. Metronidazole has been associated with neurologic toxicity at dosages of >30mg/kg.

Corticosteroids are only indicated in severe cases, with a canine that is crashing despite proper treatment with antibiotics and proper anti-protozoan therapy. Prednisone dosed at 1-2.2mg/kg PO, BID tapered over 5 days is indicated in most babesia literature.

Treatment/Cure for B. canis infections involves the use of one of two drugs. Imidocarb dipropionate (ImazolÒ, Schering Plough) is approved by the FDA and available in the United States. The only anti-babesial drug approved in the Untied States, curative for B. canis, is given in two shots two weeks apart at a dose rate of 5-6mg/kg IM or SC. Experts have reported re-dosing in 1 week if canine is still not doing well. Side effects are mostly related to cholinergic effects (Salivation, Lacrimation, Urination & Diarrhea) and pain at injection site. High doses and long term use can contribute to liver and renal damage. Pre-treatment with an anticholinergic helps reduce cholinergic effects. Diminazene aceturate (BerenilÒ, Intervet) not approved by FDA, is a curative for B. canis, also given in two shots two weeks apart at a dosage of 3-7mg/kg. Side effects are mostly related to cholinergic effects (Salivation, Lacrimation, Urination & Diarrhea) and pain at injection site. High doses and long term use can contribute to liver and renal damage. Pre-treatment with an anticholinergic helps reduce cholinergic effects. Anecdotal evidence suggests Diminazene aceturate as being a superior curative of B. canis infections when compared to Imidocarb dipropionate, with dogs recovering faster and more vitality reported since treatment.





Treatment/Cure for B. gibsoni infections involves using Azithromycin and Atovaquone in combination, this being the only drug combination to show efficacy. This treatment is shown to be effective 83% of the time, with the rest falling below sensitive PCR detection. Atovaquone is available in two forms, MepronÒ (GlaxoSmithKline) this is the single drug form, and MalaroneÒ (GlaxoSmithKline) this is the multi drug form containing Proguanil hydrochloride. The first product MepronÒ is more expensive but is very well tolerated while the latter MalaroneÒ is cheaper, and associated with sever GI side-effects. Atovaquone is a human anti-protozoal used mainly for malaria; this drug is believed to inhibit the action of cytochrome B. This treatment should always be given with a fatty meal for 10 consecutive days. Atovaquone dosage is 13.5mg/kg PO TID, while the Azithromycin dosage is 10mg/kg PO, SID, both drugs for 10 consecutive days. Some doctors believe cost will be the biggest challenge for this treatment being widely excepted.


Fluids and blood transfusions are indicated in hypovolemic, or anemic patients. Fluids best used in hypovolemic cases are colloids, while crystalloids while suffice if colloids are not available at that time. Supplementation with B vitamins into IV bag should be considered while 50% dextrose can be added to create a 5% solution if patient is hypoglycemic, or just not eating. Also IV antibiotic therapy is indicated with patients requiring fluids and/or blood transfusions, Doxycycline or Clindamycin may be used. Use of whole blood or packed RBC’s is indicated when blood transfusion is necessary with clinically anemic patients, all donors should be microscopy, IFA and PCR negative for babesiosis. Use of hemoglobin-based oxygen carrying solutions has been report with some babesiosis canines.

Clinical response usually varies from 1-2 weeks, Recheck CBC and Biochemistry’s as needed, PCR and microscopy 60 days following treatment is best test for follow up, and of course 2 consecutive tests are needed 2 weeks apart. IFA titers may persist for years following infection. Dogs infected with B. canis may be cured after treatment, while dogs with B. gibsoni have 83% cure rate, while the rest remain persistent carriers. When a dog from a multi dog household or kennel is diagnosed with babesia, then it is recommended that the entire house or kennel be screened, since both situations show a high percentage of infections. Co-infections are very possible, and should be considered with patients that fail to respond to treatment.

Currently there is only one vaccination available to a babesiosis strain. A vaccine for Babesia canis canis, it provides no cross-immunities, and is only available in Europe. Prevention mostly involves good tick control; all ticks need to be removed within 24 hours of attachment, also keeping aggressive canines away from any situation where a bite, or fight may result. Any dog previously tested positive for Babesia should be used with caution in breeding programs. Males should always be artificial collected and bitches artificially inseminated, to minimize risk of transmission during copulation.



REFERENCES

1. Birkenheuer, Adam J: Canine Babesiosis: Epidemiological, Molecular and Therapeutic Investigations. 2004, p 12-184 http://www.lib.ncsu.edu/theses/available/etd-04192004-164025/unrestricted/etd.pdf
2. Irwin, Peter J: Canine babesiosis: from molecular taxonomy to control. Parasite Vectors. 2009, March 26. doi: 10.1186/1756-3305-2-S1-S4. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2679396
3. Barr SC, Bowman DD. (2006) Five-Minute Veterinary Consult Clinical Companion Canine and Feline Infectious Diseases and Parasitology (1ST ed.). Ames, Iowa: Blackwell Publishing. p 27-33
4. Tilley LP, Smith FWK. (2008). Five-Minute Veterinary Consult Clinical Companion Canine and Feline (4th ed.). Ames, Iowa: Blackwell Publishing. p 144-145
5. Hoskins, JD: Update on babesiosis, leptospirosis in dogs, Reviewing means of transmission, latest diagnosis and treatment protocols. 2008, July 1. DVM Newsmagazine. http://veterinarynews.dvm360.com/dvm
6. Freeman MJ, Kirby BM, Panciera DL, Henik RA, Rosin E, Sullivan LJ: Hypotensive shock syndrome associated with acute babesia canis infection in a dog. 1994, Jan 1; 204(1): 94-6. J Am Vet Med Assoc.
7. Kjemtrup AM, Wainwright K, Miller M, Penzhorn BL, Carreno RA: Babesia conradae, sp. Nov., A small canine babesia identified in California. Veterinary Parasitology 2006, May 31. doi:10.1016/j.vetpar.2006.01.044. http://www.up.ac.za/dspace/bitstream/2263/1799/1/Kjemtrup_Babesia(2006).pdf.
8. Birkenheuer AJ, Neel J, Ruslander D, Levy MG, Breitschwerdt EB: Detection and molecular characterization of a novel large Babesia species in a dog. Veterinary Parasitology 2004, Oct 5. http://www.ncbi.nlm.nih.gov/pubmed/15381295
9. Van de Maele I, Savary-Bataille K, Gielen I, Daminet S: An unusual form of canine babesiosis. Canadian Veterinary Journal 2008, March. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2249724
10. Bashir N, Chaudhry ZI, Ahmed S, Saeed MA: Epidemiological and vector identification studies on canine babesiosis. Pakistan Veterinary Journal 2009. http://pvj.com.pk/pdf-files/29_2/51-54.pdf
11. Sodikoff/, CH. (1995). Laboratory Profiles of Small Animals (2nd ed) St. Louis, Missouri: Mosby Publishing. p. 394-395
12. Lin MY, Wu SY, Huang HP: Treatment for canine Babesiosis: 40 cases. VIN 2007, August. http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2007&Category=2971&PID=18313&O=Generic
13. Jefferies R, Ryan UM, Jardine J, Broughton DK, Robertson ID, Irwin PJ. Blood, bull terriers and babesiosis, a review of canine babesiosis. Australian Veterinary Journal 2007, November. http://www.ncbi.nlm.nih.gov/pubmed/17970851?dopt=Abstract&holding=f1000,f1000m,isrctn
14. Birkenheuer AJ, Correa MT, Levy MG, Breitschwerdt EB: Geographic distribution of babesiosis among dogs in the United States and association with dog bites: 150 cases (2000–2003). J Am Vet Med Assoc 2005, September 15. http://www.ncbi.nlm.nih.gov/pubmed/16190594

 

Yea these lecture notes are on here twice already. I posted them on 2/3/09 this year. These notes are from the NAVC (North American Veterinary Conference) I attended this past Jan in Orlando. I posted it on 2 forums (including this one). But I took out the dosages for the medication.

http://www.game-dog.com/forums/showthread.php?t=30979