Recent advances in canine leptospirosis: focus on vaccine development

Figures & data

Table 1 Overview of most common serogroups in dogs in different geographical regions and periods based on serological data published between 1973 and 2014

Geographic region	Country	Reference	Year(s) of investigations	Number of sera, % positivea	Predominant serogroups, expressed in % of seropositive dogsb	Remarks
Europe	Scotland	^Citation91	≤1973	120, 39%	Can, 79%; Ict, 11%	Vaccinated and non-vaccinated urban dogs
	Germany	^Citation92	≤1974	347, 13%	Grip, 56%, Ict, 15%; Sej, 15%	Different service and working breeds
	Ireland	^Citation93	≤1974	446, 34%	Can, 50%; Ict, 46%	Urban and suburban dogs
	the Netherlands	^Citation38	1969–1982	1,289, 10%	Ict, 76%; Can, 24%	Serum samples submitted for MAT
	Germany	^Citation94	1985–1988	993, 31%	Grip + Aus, 28%; Sej, 3%	South Bavaria
				408, 33%	Grip + Aus, 18%; Sej, 6%	North Bavaria and other regions
	Italy	^Citation95	≤2002	245, 29%	Aus, 36%; Gri, 19%; Can, 11%; Ict, 8%	Privately owned dogs and kenneled dogs (most stray dogs)
	Greece	^Citation96	≤2003	254, 12%	Ict	Randomly selected serum samples
	Germany	^Citation97	1999–2002	3,671, 42%	Ict; Gri; Can; Aus; Sejc	Serum samples submitted for MAT by veterinary practitioners
	France	^Citation98	≤2006 (5-year period)	2,457, N/A%	Ict, Aus, Sej, Can, Gric	N/A
	Germany	^Citation99	1990–2003	42, 100%	Gri, 31%; Sej, 24%; Ict, 17%; Can, 12%; Aus, 7%	Dogs diagnosed with leptospirosis
	Germany	^Citation100	2003–2006	39, 100%	Ict, 26%; Aus, 26%; Sej, 8%; Gri, 5%; Pom, 5%	Dogs diagnosed with leptospirosis
	France	^Citation101	2003–2008	37, 100%	Ictc	Dogs suspected of leptospirosis
	the Netherlands	^Citation102	2003	86, 74%	Ict, Canc	Healthy dogs
			2003	26, 85%	Ict, Ausc	Non-vaccinated dogs in hunting pack
			2009	100, 37%	Ictc	Dog sera submitted to commercial labs
	Switzerland	^Citation103	2007–2008	52, 100%	Aus, Gri, Pom, Aut, Ictc	Dogs diagnosed with leptospirosis
	Germany	^Citation104	2006–2011	329, N/A%	Aus, 24%; Gri, 20%; Pom, 9%	Dogs suspected of leptospirosis
	Switzerland	^Citation24	2003–2012	298, 44%	Aus, Gri, Pom, Autc	Dogs suspected of leptospirosis
	France	^Citation105	2008–2011	232, 100%	Aus, Gric	Dogs diagnosed with leptospirosis
North America	Canada	^Citation106	≤1976	619, 6%	Aut, 40%; Can, 30%	600 stray dogs; 19 patients
	USA	^Citation107	≤1980	433, 38%	Ict	Urban stray dogs
				123, 19%	Ict	Suburban stray dogs
	Canada	^Citation108	≤1991	474, 39%	Can + Ict, 14%	Dog sera submitted for MAT:
					Can, 10%; Ict, 10%; Aus, 3%	Likely post-vaccination titers
						Post-infection titers
	Canada	^Citation22	1998–2001	462, 26%	Aut (paradoxical)	Dog sera submitted for MAT
	Canada	^Citation109	1996–2001	1,260, 29%	(≥1:800) Gri; Ausc	Dog sera submitted for MAT
				15, 100%	(≥1:800) Gri, 100%	Dogs diagnosed with leptospirosis
	USA	^Citation110	2001	500, 21%	Gri; Ict; Canc	Privately owned dogs and patients
	USA	^Citation111	1997–2002	470, 11%	Gri, Aus, Ict, Pomc	Dog sera submitted for MAT
				34, 100%		Dogs diagnosed with leptospirosis
	USA	^Citation112	1999–2001	950, 23%	Gri, 14%; Aus, 6%	Healthy vacc dogs
				291, 30%	Gri, 13%; Can, 8%; Aus, 4%	Healthy non-vacc dogs
	USA	^Citation113	1998–2000	43, 100%	Pom, 40%; Can, 9%; Aus, 5%; Gri, 5%	Dogs diagnosed with leptospirosis
	USA	^Citation114	2000–2007	33,119, 8%	Gri, Pom, Aus, Autc	Dog sera submitted for MAT
South, Central	Argentina	^Citation115	≤1980	143, 51%	Can, 37%; Pyr, 5%; Aut, 2%	Stray dogs
America;	Chile	^Citation116	≤1996	25, 28%	All dogs:	Dogs diagnosed with leptospirosis
Caribbean				12, 17%	Can, 36%; Pyr, 27%	Dogs with other diagnosis
				13, 61%		Dogs without diagnosis
	Barbados	^Citation117	≤1997	48, 62%	Aut, 22%; Ict, 8%; Aus, 8%	Healthy control dogs
				46, 75%	Ict, 36%; Aus, 13%; Aut, 8%	Acutely ill dogs
	Eight countries in this region	^Citation118	2002–2014	Per reviewed study:,100 to .400, N/A%	Depending on country: Ict, Can, Aut, Tar, Aus, Gri, Pom, Sej, Louc	Different categories of dogs
Asia, South	Australia	^Citation119	1971–1972	600, 7%	Ict, 73%; Pom, 15%	Dogs from Sydney
Pacific	Fiji	^Citation120	≤1984	100, 57%	Bal, 12%; Aus, 11%; Ict, 5%	N/A
	Micronesia	^Citation121	1995–1996	Unclear	Aus (serovars Aus and Bra)	Majority dogs: farm dogs
	New Zealand	^Citation122	≤2002	466, 14%	Ict, 62%	Healthy dogs (lower North Island, New Zealand)
	Taiwan	^Citation123	2004	241, 46%	She, Can, Aus, Ictc	Stray dogs
	Thailand	^Citation124	2004	210, 11%	Bat, Can, Aus, Ictc	Randomly selected dog sera (university hospital)
	Australia	^Citation125	≤2008	956, 1.9%	Bal, 39%; Ict, 22% (percentages of 18 seropositive dogs)	Dogs from different regions in Australia
	Japan	^Citation126	2006–2007	801, 27%	Ict; Autc	Patients from vet clinics from all 47 prefectures
	Japan	^Citation127	2007–2011	58, 52%	Heb, Aus, Autc	Dogs suspected of leptospirosis
	India	^Citation128	2006–2008	40, 18%	Pyr, 100%	Dogs suspected of leptospirosis
Africa; Middle	Egypt	^Citation129	≤1973	50, 12%	Can, 83%; Ict, 17%	Stray dogs
East	Turkey	^Citation130	≤2005	116, 44%	Aus, Canc	Healthy stray dogs
	Nigeria	^Citation131	2005–2006	52, 100%	Gri, Aus, Pomc	Privately owned dogs suspected of leptospirosis
	South Africa	^Citation132	2008–2009	530, 5%	Can, Pyrc	Privately owned dogs and stray dogs
	Zimbabwe	^Citation133	≤2012	250, 16%	Not tested (ELISA used instead of MAT)	Randomly selected urban dogs
	Uganda	^Citation134	2011	105, 27%	Ict, Can, Pyrc	Privately owned rural dogs

a Notes: Percentage of seropositive dogs, with criterion for seropositivity (MAT cut-off) varying between studies from 1:20 to 1:400 in healthy dogs, and from 1:100 to 1:3,200 in dogs with acute leptospirosis;

b mixed reactions with same titers against different serogroups not included;

c percentages with predominant serogroups not given.

Abbreviations: MAT, microscopic agglutination test; ELISA, enzyme-linked immunosorbent assay; Can, Canicola; Ict, Icterohaemorrhagiae; Gri, Grippotyphosa; Sej, Sejroe; Aus, Australis; Bal, Ballum; Pom, Pomona; Aut, Autumnalis; Pyr, Pyrogenes; Tar, Tarassovi; Heb, Hebdomadis; Bat, Bataviae; She, Shermani; Bra, Bratislava; Lou, Louisiana; pos, positive; N/A, not available; vacc, vaccinated; non-vacc, not vaccinated.

Table 2 Clinical characteristics of canine leptospirosis

Clinical presentation	Reported frequency of clinical signs	Clinical signs	References
Peracute (<24 hours; rarelydiagnosed)a	Most frequent	Either sudden death or death preceded by few clinical signs, eg, lethargy/depression, anorexia	^Citation9,Citation32,Citation38,Citation135^–^Citation137
	Less frequent	Lethargy/depression, anorexia, vomiting, diarrhea
Acute (1–2 days; not often diagnosed)	Most frequent	Lethargy/depression, anorexia, vomiting, muscle weakness, myalgia, death	^Citation9,Citation32,Citation33,Citation38,Citation39,Citation48, ^Citation135^–^Citation140
	Less frequent	Fever, hypothermia, diarrhea, dehydration, PUPD, jaundice, red eyes, intestinal invaginations
Subacute (2–7 days; most common form of diagnosed cases)	Most frequent	Lethargy/depression, anorexia, vomiting, fever, hypothermia, dehydration, polyuria and polydipsia, abdominal pain on palpation, diarrhea	^Citation6,Citation9,Citation32,Citation33,Citation36,Citation38,Citation39, ^Citation48,Citation135^–^Citation140
	Less frequent	Intestinal invaginations, weight loss, muscle weakness, myalgia, coughing, dyspnea, jaundice, pale mucous membranes, petechiae, abortion, death
Chronic (> 1 week; not often diagnosed)	Most frequent	polyuria and polydipsia, jaundice, weight loss, emaciation, anterior uveitis	^Citation6,Citation28,Citation36,Citation137
	Less frequent	Petechiae, hemoptysis, ascites, abortion, death
None = subclinical leptospirosis (probably majority of infected dogs)	Not applicable	Not applicable	^Citation25,Citation137

Note:

a Time after commencement of clinical signs.

Abbreviation: PUPD, polyuria/polydipsia.

Figure 1 Kidney cortex, transverse section through convoluted tubules, Warthin-Starry staining (magnification 400×).

Notes: Dog from non-vaccinated control group challenged with serovar Canicola. White arrow indicates massive presence of leptospires in lumen of convoluted tubule; black arrows indicate mononuclear infiltration.

Table 3 Treatment strategies in different clinical presentations of canine leptospirosis

Speed of onset and progress of clinical signs	Affected organ system	Pathology and disorders	Antibiotic therapy^Citation6	Supportive therapy^Citation6,Citation47,Citation48,Citation141^–^Citation143
				aIntravenous fluid replacement therapy/dialysis	Other treatments
Peracute, acute, subacute	Liver	Acute hepatitis	Vomiting/diarrhea (ie, oral medication not effective): ampicillin, 20 mg/kg BW IV every 6 hrs for 2 wks or penicillin G, 25,000–40,000 U/kg	Hypoalbuminemia: plasma or colloids	N/A
	Kidneys	Acute interstitial nephritis, acute renal failure, uremia (also known as azotemia)		Lactate Ringer’s solution (≥60 mL/kg BW/day)	Pain medication: buprenorphine, 0.01 mg/kg BW IV every 6 hrs
				Oliguria: idem with diuretics (eg, furosemide or mannitol)
				Severe anuria: hemodialysis; hypoalbuminemia: plasma or colloids
	Lungs	Pulmonary hemorrhages, lung edema	BW IV every 12 hrs for 2 wks After vomiting/diarrhea have subsided: doxycycline, 5 mg/kg	Pulmonary edema (secondary): plasma or colloids	Pulmonary hemorrhages: oxygen therapy (eg, with nasal tube) If severe: mechanical ventilation
	Gastro-intestinal tract	Acute gastritis, acuteenteritis, intestinal intussusception	BW orally every 12 hrs for 2 wks No vomiting/diarrhea: doxycyclin, 5 mg/kg BW orally every 12 hrs for 2 wks	N/A	Uremic gastritis/vomiting: histamine receptor blockers or proton pump inhibitors, orally Intestinal intussusception: manual reduction or intestinal resection Pain medication: buprenorphine, 0.01 mg/kg BW IV every 6 hrs
	Blood vessels, blood	Vasculitis, thrombocytopenia, disseminated intravascular coagulation, hemorrhages		Coagulation disorders: whole blood or plasma	N/A
Chronic	Liver	Chronic hepatitis	When dog is still leptospiruric: doxycycline, 5 mg/kg orally every 12 hrs for at least 2 wks	N/A	N/A
	Kidneys	Chronic interstitial nephritis, chronic renal disease		Hypertension: antihypertensive agents (either against renin- or volume-dependent hypertension) Hypokalemia, hyperphosphatemia: treatment with phosphate-binding salts (preferably calcium)	N/A
	Lungs	None		N/A	N/A
	Gastro-intestinal tract	Chronic (uremic) gastritis, chronic enteritis		N/A	Uremic gastritis/vomiting: histamine receptor blockers or proton pump inhibitors, orally Prolonged inappetence: enteral or parenteral nutrition
	Blood vessels, blood	None		N/A	N/A

Note:

a Caveat: life-threatening fluid overload must be prevented.

Abbreviations: BW, body weight; IV, intravenous; hrs, hours; wks, weeks; N/A, not applicable; idem, Lactate Ringer’s solution.

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