Leptospirosis

Question 1

describe leptospira (4)

Answer 1

1. gram negative spirochete
2. 20 species (interrogans is most medically important)
   -super tiny, not easy to stain and see
3. maintained in wildlife and domestic hosts: rodents, swine, dogs
4. can be chronically shed and can survive in water or urine-soaked soil for days to months
   -ALL are potentially zoonotic!!!

Question 2

describe pathogenic features of leptospira

Answer 2

1. pore-forming hemolysins (sphingomylinases):
   -damage host membranes
   -may cause intravascular hemolysis
2. LPS (endotoxin)
   -contributes to inflammation/platelet activation, neutrophil adherence, and coagulation abnormalities
3. cytotoxin: damages platelets (leads to thrombocytopenia/possible hemorrhage)

Question 3

describe transmission of leptospira

Answer 3

1. maintenance hosts: rodents, swine, and dogs, harbor the bacteria but remain asymptomatic
2. incidental hosts: dogs, horses, cattle
   -infected by directly contacting URINE, or venereal or placental transfer, or contact with infected tissue or with contaminated water, soil, or feedstuffs

Question 4

describe pathogenesis of leptospira

Answer 4

1. infection:
   -enter via skin abrasions or mucous membranes!! of mouth/eyes/nose
   -can lead to systematic spread
2. proliferates in:
   -kidney
   -liver
   -spleen
   -CNS, eyes
   -genital tract
3. can cause:
   -subclinical disease
   -reproductive disease (abortions)
   -intravascular hemolysis
   -damaged capillary endothelium, resulting in hemorrhage
   -recurrent uveitis (horses)
   -acute renal failure

Question 5

describe canine leptospirosis

Answer 5

1. serovars: icterohemorrhagiae, grippotyphosa, pomona, australis, bratislava, canicola (dog-adapted, milder disease)
2. seasonal incidence: late summer/early fall with links to rainfall and flooding
   -patterns depending on regional climate
3. higher risk in:
   -dogs with access to outdoor water sources/wildlife
   -males. herding dogs, hounds, working dogs
   -but can be seen in any dog! even a small indoor white fluffy one bc rodents are everywhere

Question 6

describe clinical presentation of leptospirosis in dogs

Answer 6

1. fever, depression
2. lethargy
3. loss of appetite
4. joint or muscle pain
5. vomiting, diarrhea
6. cough
7. changes in urination

Question 7

describe clinical presentation of leptospirosis in cats

Answer 7

they don’t care
rarely show signs

Question 8

describe clinical presentation of leptospirosis in horses

Answer 8

1. fever
2. uveitis
3. abortion
4. acute renal failure

Question 9

describe clinical presentation of leptospirosis in cattle

Answer 9

1. abortion
2. stillbirth
3. birth of weak offspring
4. infertility
5. bloody milk

Question 10

describe pathogenic mechanisms of leptospirosis

Answer 10

incubation period can be 2-25 days

1. after entering the host, leptospires spread hematogenously
   -no fulminant septic disease (low endotoxic potential of their LPS)
2. leptospiremia develops until hose develops acquired immunity response clears bloodstream/most tissues
3. leptospires can persist in immune-privileged sites (eyes and renal tubules)
4. multisystemic disease affecting primarily the kidneys, liver, and sometimes lungs in dogs
   -many other organs/tissues can e infected: spleen, endothelium, uvea/retina, heart, muscles, meninges, pancreas
   -vasculitis is a feature of the disease

Question 11

describe leoptospirosis pathogenic mechanisms in the kidney

Answer 11

1. acute phase of infection: acute interstitial nephritis with tubular cell necrosis
2. glomerular structural abnormalities are also described
3. hyposthenuria can occur due to nephrogenic diabetes insipidus

Question 12

describe clinical presentation in acute disease

Answer 12

1. nonspecific signs
   -in dogs usually related to renal failure and/or hepatic injury
   -anorexia, vomiting, diarrhea, jaundice, fever
   -PU/PD or oligoanuria
   -pulmonary bleeding common in some areas
2. clinic disease in cats is possible, but rare, and cats can carry leptospires and be asympotmatic so is difficult to prove casuality

Question 13

describe chronic disease of leptospirosis

Answer 13

potential role in chronic active hepatitis and chronic kidney disease in survivors

Question 14

describe clinical pathology for diagnosis of leptospirosis

Answer 14

following can occur but not all must be present

1. mild to moderate anemia: GI or pulmonary bleeding in about 50% of dogs
2. neutrophilic leukocytosis with left shift
3. mild to severe thrombocytopenia
4. azotemia
5. liver enzyme elevation (ALP >ALT)
6. hyperbilirubinemia
7. electrolyte abnormalities (due to AKI)
8. hemostatic disorders (hypor or hypercoagulable)
9. isosthenuria (majority) to hyposthenuria
10. glucosuria
11. glomerular or tubular proteinura
12. hematuria
13. pyuria
14. granular casts

AKA kidney or liver, hella unspecific

Question 15

describe diagnostic imaging of lepto

Answer 15

1. pulmonary changes (lepto lung)
   -interstitial or alveolar pattern
   -mild mediastinal or pleural effusion
2. renal changes (all non specific)
   -renomegaly
   -renocortical hyperechogenicity
   -mild pyelectasia
   -medullary band signs of hyperechogenicity
   -mild perineal fluid accumulation
3. other: hepatomegaly, splenomegaly

Question 16

describe how to confirm a diagnosis of lepto

Answer 16

1. you can test for either antibodies (serum) or antigen (blood, urine, or tissues)
2. timing:
   -initially blood is super high for antigen, then as days progress, antigen in blood is reduced so no antigen increases in urine with shedding
   -now antibodies until a couple days post infection
3. gold standard!!! for acute lepto!!
   -microagglutination test
   -evaluates antibodies against different serovars
   -specific, sensitive, and widely available: results can be affected by vaccine-induced antibodies (typically low titers) so always ask if vaccinated for lepto!! will see a low titer for vaccine serovars if so

-difficult to standards and requires live cultures so takes about a week

-cross-reactivity is common: highest titer is the infecting serovar though

-can use convalescent titers to confirm diagnosis: retest in 1-2 weeks and assess for at least a 4-fold rise in titers to confirm acute infection
-vaccine titers would NOT increase by 4 fold!

4. point of care tests: ELISA and lateral flow assays
   -detect IgG and/or IgM
   -patient side tests, but less accurate
   -best used in conjunction with other tests like MAT
5. PCR:
   -because exact timing of infection is unknown, it is best to perform on both blood and urine
   -several assays described: diagnostic performance of all PCR assays is not equivalent
   -some can do molecular typing
   -false positives and negatives are possible!!
   –results CAN be affected by antibiotics!! best to collect samples before starting therapy but can still test after
   -best to combine with MAT

Question 17

describe treatment of leptospirosis

Answer 17

1. antimicrobials:
   -penicillins: reduce leptospiremia but fail to reliably clear the organisms from the kidney; good choice initially for animals that might not tolerate doxycycline

-doxycycline: clears the leptospires from tissues; often not well-tolerated in the early treatment due to GI side effects

2. supportive care: for AKI, hepatopathy, etc.

prognosis: some animals can do really well with appropriate treatment!!

Question 18

describe lepto prevention

Answer 18

vaccination!!

1. is a now a core vaccine so ALL dogs are at risk so recommend to vax all dogs annually
2. bivalent vaccines (serovars canicola and icterohaemorrhagiae) confer only partial or no immunity to heterologous serogroups such as Australis, grippotyphosa, and pomona
3. quadrivalent vaccines: all 4 of above serovars; have been available in US since 2001 and are PREFERRED