Some of your questions answered from the Leptopspirosis Webinar….

Following on from the fantastic webinar presented by Catherine Bovens on Leptospirosis there we just too many questions to get through on the  live webinar so Catherine has very kindly gone through and answered them all.  Some of the questions are more relevant for Michelle Townley from MSD to answer so we will upload those answers when we have then.

 

Catherine Bovens

Q1: Can mice be carriers or just rats?

C: Multiple species act as maintenance hosts and can carry leptospires. Rats are the maintenance host of the icterohaemorrhagiae serovar. But other small rodents such as mice and voles, hedgehogs, foxes and wild boars can all carry leptospires, as well as cattle and pigs.

 

Q2: In a chronic hepatitis case caused by Leptospirosis will you still have a raised antibody level? If several months since the condition started is it still worth doing antibody test?

C: In an animal affected for several months, I would expect an immune response to have occurred with production of antibodies, so an MAT serology test should be a good screening test. However false negative results remain possible if the animal has not been able to produce antibodies, for example immunosuppressed animals. In a paper describing chronic hepatitis associated with leptospiral infection in vaccinated Beagles (reference: Adamus et al., J Com Path 1997, vol 117, p. 311-328), 11 Beagles with chronic hepatitis were demonstrated to be infected with leptospires in their liver via immunohistochemistry, special staining or culture; these dogs had poor and inconsistent serological responses, and one hypothesis was that the leptospires may have been sequestered in bile canaliculi and exerting little antigenic stimulation. So overall, in a dog with chronic hepatitis, I would do an MAT serology but I would also ask the laboratory to look for leptospires on a liver biopsy, if possible with fluorescence in-situ hybridisation or PCR, or at the minimum with special staining.

 

Q3: Would an insurance company cover the costs of treatment in an in-contact dog?

C: I am not sure. The insurance company may be more likely to cover costs of treatment if seroconversion can be documented on paired MAT titres, as exposure and risk of disease is then documented in that specific dog. But this would be a question best asked to the insurance company. As treatment with 2 weeks of doxycycline is relatively cheap and could prevent a disease that could be very expensive to treat, I’d say that it would be a good investment from the insurance company perspective.

 

 

Q5: Should we be considering vaccinating cats against leptospirosis?

C: At this stage, we have only rare reports of clinical leptospirosis in cats and some data indicating that outdoors, hunting cats can be carriers. It is not enough evidence to justify vaccination in pet cats. There is also no vaccine currently licensed in cats. However, I would consider testing for leptospirosis in an outdoor, hunting cat with acute or acute-on-chronic renal disease.

 

Q6: Do you think that we should be testing healthy dogs and cats more routinely for leptospirosis?

C: This is a difficult question to answer. We know that healthy dogs and cats can shed leptospires in their urine, possibly putting humans at risk. For dogs, if they are appropriately vaccinated with a vaccine that has been shown to prevent renal carriage, the risk of excretion of infectious leptospires should be low and I would not recommend routine testing. For cats, the study looking at excretion of leptospires in urine was in stray and feral cats, and we don’t know how frequent carriage is in normal pet cats; routine testing at this stage is difficult to justify. I would potentially consider a urine PCR test for Leptospira for animals with immunosuppressed owners at significant risk of infection, or for animals used for hospital visits or water activities with humans.

 

Q7: When does seroconversion begin? When do IgM begin to be produced?

C: In experimental studies, the IgM as measured via ELISA increases within one week after initial infection, and the maximum titre develops within 2 weeks. Increased IgG titres as measured via ELISA develop 2 to 3 weeks after infection, with a maximum titre within approximately one month. However in general, the MAT serological test is considered superior in overall sensitivity and specificity to serologic assays based on ELISA, so use of ELISA is not recommended in practice. The Microscopic Agglutination Test (MAT) measures agglutinating antibodies consisting mainly of IgM as well as some IgG (reference: Chapter 42, Leptospirosis of the textbook Infectious Diseases of the Dog and Cat, 4th edition, editor C. E. Greene, p. 431-447). In the first week of illness, dogs frequently have negative MAT results, although seroconversion can occur as early as 3-5 days after dogs are brought to a veterinarian (reference: Sykes et al., 2010 ACVIM Small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment and prevention. J Vet Intern Med 2011, 25:1-13). A point-of-care lateral flow assay has been developed for the detection of IgM in serum and appears promising for the diagnosis of acute leptospirosis, but it has not been widely evaluated yet in veterinary medicine (reference: Abdoel et al., Rapid test for the serodiagnosis of acute canine leptospirosis. Vet Microbiol 2011, 150:211-213). Such a test has the advantage of allowing immediate results and may be positive earlier in the course of the disease than the MAT. This test should be assessed with a larger number of serovars before its use can be recommended in practice.

 

Q8: In those dogs with non renal or hepatic symptoms eg those with respiratory or neurological symptoms, do many have renal or hepatic changes on serum biochemistry?

C: All the studies in dogs so far were performed to detect pulmonary disease in dogs with a diagnosis of leptospirosis (references: see end of this reply). Most or all of the dogs in these studies had renal or hepatic involvement and were diagnosed with leptospirosis due to these. However as far as I know, there have not been any studies looking at dogs with pulmonary disease without renal or hepatic involvement to find out which proportion of those dogs have leptospirosis. We know that in humans, the severe pulmonary form of leptospirosis (haemorrhagic pneumonitis) can occur without hepatic or renal involvement (reference: Lung 2011, see below). It presents as acute respiratory distress, dyspnoea, chest pain, and/or coughing with haemoptysis and has a high mortality rate. I suspect that leptospirosis may be underdiagnosed in dogs with solely pulmonary manifestations, due to lack of clinician awareness, and also as the clinical signs may be acute and severe and dogs with pulmonary disease may die before a diagnosis is reached.

For dogs with neurological signs this is even more difficult to tell, as neurological signs remain a rare presentation of leptospirosis in dogs.

 

References:

–       Baumann et al. Radiographic findings in the thorax of dogs with leptospiral infection. Vet Radiol Ultrasound 2001, 42(4):305-307.

–       Klopfleish et al. An emerging pulmonary haemorrhagic syndrome in dogs: similar to the human leptospiral pulmonary haemorrhagic syndrome? Vet Med Int 2010, doi:10.4061/2010/928541.

–       Kohn et al. Pulmonary abnormalities in dogs with leptospirosis. J Vet Intern Med 2010, 21:1277-1282.

–       Gendron et al. Serial CT features of pulmonary leptospirosis in 10 dogs. Vet Rec 2014, Feb 15;174(7):169.

–       Marchiori et al. Clinical and imaging manifestations of hemorrhagic pulmonary leptospirosis: a state-of-the-art review. Lung 2011, 189:1-9.

 

Q9: Can we assume that all leptospirosis vaccines prevent renal carriage?

C: No, only some vaccines have been proven to protect against renal carriage in dogs. Many vaccines are only licensed to prevent clinical disease. Nobivac L4 protects against renal carriage from Canicola, Icterohaemorrhagiae and Grippotyphosa serogroups. Nobivac L4 has not been approved to reduce renal carriage by the serogroup Australis (including serovar bratislava), so although vaccinated dogs should be protected against developing disease from this serogroup, asymptomatic renal carriage cannot be excluded for this serogroup.

 

Q10: Are all serovars zoonotic?

C: All the serovars that typically cause infection in dogs in Europe are zoonotic.

 

Q11: How long after starting antibiotics is the zoonotic risk reduced?

C: We don’t know; no published studies document the duration of shedding of leptospires in canine urine after antibiotic therapy. Based on rodent model studies, viable leptospires are likely to still be present in the urine within the first 2-3 days of treatment (reference: Sykes et al., 2010 ACVIM Small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment and prevention. J Vet Intern Med 2011, 25:1-13). However in one paper, there was evidence of ongoing shedding of high numbers of spirochaetes in the urine after seven days of oral treatment with doxycycline, at which time the dog was clinically back to normal (reference: Juvet et al. Urinary shedding of spirochaetes in a dog with acute leptospirosis despite treatment. Vet Rec 2011, May 28;168(21):564).

Urinary PCR is useful following treatment to ensure that the organisms have been eliminated from the kidneys. A positive result does not always mean that viable leptospires are present in the urine, as dead leptospires may be detected following antibiotic treatment. False-negative results may occur as urinary shedding of leptospires can be intermittent. However PCR is currently the best test available for urinary shedding. For safety reasons, it is recommended to observe appropriate handling precautions in case of a positive result and to consider further antibiotic treatment with doxycycline until the urinary PCR becomes negative (reference: Sykes et al., 2010 ACVIM Small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment and prevention. J Vet Intern Med 2011, 25:1-13).

Q12: Which dose of doxycycline is usually used?

C: The recommended dose for doxycycline for the treatment of leptospirosis is 5 mg/kg orally every 12 hours for 2-3 weeks. The optimal duration of antibiotic therapy has not been determined. The recommendation is to perform urinary PCR following antibiotic treatment, and to continue doxycycline until the PCR is negative (see above question) (reference: Sykes et al., 2010 ACVIM Small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment and prevention. J Vet Intern Med 2011, 25:1-13).

Q14: Could you please advise on the actual numbers of cases at AHVLA rather than percentages, to get a better feel for overall incidence in the UK.

C: Unfortunately I don’t have this data. It should be noted that other laboratories offer serological or PCR testing for leptospirosis, so the total number of positive samples at the AHVLA would not correspond to the total number of cases of leptospirosis in dogs in the UK.

 

Q15: How does the cost of MAT serology and PCR compare? 

C: At the laboratory where I usually submit my samples, the costs are £67.20 for an MAT serology, and £60 for a PCR (excluding VAT).

Q16: Do you get dogs that solely show respiratory signs or would you always expect to see some evidence of renal or liver issues too?

C: See question 8.

 

Q17: Did you run clotting factors before doing the biopsy?
C: Yes, I always check a platelet count and coagulation times before all liver biopsies.

 

Q18: Have you seen leptospirosis in any exotics?

C: I don’t see exotics at all, so my experience is very limited. From a rapid search of the literature, leptospirosis can affect hamsters, guinea pigs and rabbits, and most mammals can probably be affected.

Q19: What dose of amoxicillin-clavulanate would you use for the treatment of leptospirosis?

C: I would use amoxicillin-clavulanate 20 mg/kg intravenously every 6-8 hours. Penicillin G can also be used as an injectable antibiotic if amoxicillin-clavulanate is not available (dose: 25,000–40,000 units/kg IV or IM q12h). These antibiotics will NOT clear the renal carrier status and it is essential that a course of doxycycline is administered afterwards. Once the dog can tolerate oral medication, I would change to doxycycline (see question 12 for dose).
Q20: Is leptospirosis transmissible to exotic pets?

C: See questions 18.

 

Q21: Intranasal administration of Parainfluenza uptake can be low and DHP is used with L4. What level of risk is perceived about the increase in parainfluenza incidence?

C: Both vaccinations against canine parainfluenza and leptospirosis are non-core vaccines and vaccination of an individual dog should be based on risk assessment. I would say that in the UK, dogs may well be exposed to both. Parainfluenza alone should only cause a self-limiting cough with laryngitis, tracheitis, and possibly a serous nasal discharge; the clinical signs should resolve spontaneously. However co-infection with Bordetella bronchiseptica or another respiratory viruses, especially in puppies, can cause an extended and potentially serious clinical disease, so vaccination is usually recommended. Leptospirosis can be life-threatening. So ideally a dog in the UK should be vaccinated for both leptospirosis and parainfluenza, especially puppies. If only one vaccine can be given, I’d base my choice on the lifestyle of the dog (exposure to rodents/wildlife, hunting, living in a rural location and access to water increase the risks of leptospirosis; canine parainfluenza virus is usually transmitted with direct contact with an infected dog, so meeting lots of other dogs increases the risk of parainfluenza infection).

An intranasal vaccine should be preferred rather than a subcutaneous injection for parainfluenza as local mucosal immunity is most important in protecting dogs from infection, and intranasal vaccines will give a better local immunity. I would highly recommend using an intranasal vaccine for parainfluenza and a parenteral vaccine for leptospirosis.

 

Q22: Would there be a need for the Nobivac L4 vaccine in the highlands of Scotland?

C: It is difficult to tell as I cannot find any data on the seroprevalence or disease incidence in dogs in Scotland. If you see cases of leptospirosis in dogs vaccinated with a bivalent leptospirosis vaccine, it is likely that non-vaccinal serogroups are present in the area. I would also consider that more and more people travel with their dogs for holidays etc, and we know that there are serogroups other than Icterohaemorrhagiae and Canicola in England and many other European countries, so I would recommend a quadrivalent vaccine for any dog that may travel outside of Scotland.

 

Q23: Do adult dogs need two vaccine injections at boosters?

C: For the Nobivac L4, adult dogs need two injections when they receive the L4 for the first time, then after that it is one injection yearly.

 

Q24: If in-contact dogs need treatment, do in-contact humans also need treatment, including vets & nurses? Are most vets protected by vaccine syringe stick injuries?

C: I cannot really recommend human healthcare measures. But I have never been treated prophylactically. The numbers of vets with antibodies against Leptospira in studies remain low, and disease transmission is unlikely if strict barrier nurse is applied. Also doxycycline can have unpleasant side effects in humans (gastrointestinal mostly). At my clinic, we warn all staff and clients who have been in contact with a dog suspected to have leptospirosis or diagnosed with leptospirosis that they should contact their GP and tell them about it if they become ill in any way, particularly with flu-type signs. But we don’t recommend seeing their GP if they remain healthy. I once got the flu myself 2 weeks after contact with a dog with leptospirosis, and I was tested for leptospirosis (negative) and treated with doxycycline, but that was because I had clinical signs.

I think that a needle stick injury with a syringe containing a vaccine for leptospirosis is very unlikely to give a human a sufficient dose of antigen to be protected against leptospirosis. Canine vaccines have not been assessed in humans, so even injection of a full dose may not induce immunity in a human.

 

Q25: What would be an ideal vaccination schedule for a puppy?

C: This is a tricky question and I would base myself on recent published vaccination guidelines such as the WSAVA guidelines rather than vaccine manufacturer recommendations. The WSAVA vaccination guidelines, as well as a summary for owners, can be accessed for free (http://www.wsava.org/guidelines/vaccination-guidelines). Below are my recommendations for a normal companion puppy in the UK. Other recommendations would apply in higher risk situations (shelters, breeders, kennels, hunting dogs) or different locations.

 

In the vaccine guidelines from the WSAVA, it is recommended that puppies should have their last puppy vaccination at 14-16 weeks of age (same for kittens), then first booster at one year. A number of puppies receiving their last vaccine at 10 or 12 weeks will actually not be covered until their 1-year booster, due to maternal antibodies. Very few practices in the UK seem to follow those guidelines though, and we don’t seem to see that much parvovirosis in vaccinated puppies that finish their vaccines at 10 or 12 weeks, but that doesn’t mean that these puppies are appropriately protected. Distemper and adenovirus hepatitis are rare (although there were a couple of cases of distemper in some puppies in Wales recently), but again puppies receiving their last vaccine at 10 or 12 weeks may not be appropriately protected.

If I had to devise a vaccine protocol for puppies in the UK, I’d vaccinate at 8, 12 and 16 weeks for all the viruses (distemper, hepatitis and parvovirus, DHP). If a puppy comes in at 6 weeks, I’d probably either wait until 8 weeks to vaccinate (do worming and flea treatments etc only at 6 weeks), or vaccinate at 6, 12 and 16 weeks (6 weeks instead of 8), unless they are at high risk (living in a kennel or shelter, or outbreak of parvovirosis/distemper in the area), in which case I’d do DHP every 2 weeks until 14-16 weeks old.

 

For leptospirosis, I would use a quadrivalent vaccine (ie Nobivac L4). The WSAVA guidelines recommendations are to vaccinate initially at 12-16 weeks for leptospirosis, with a second dose 3-4 weeks later. So I would vaccinate at 12 and 16 weeks for leptospirosis. Vaccination against leptospirosis could potentially be done at 6 or 8 weeks, then at 12 and 16 weeks (so starting earlier and with 3 injections) if the risk of exposure is high (leptospirosis outbreak in the area).

 

For kennel cough, I would recommend using an intranasal vaccine containing parainfluenza and Bordetella bronchiseptica (intranasal vaccines are recommended to give better local mucosal immunity), and I would vaccinate puppies at 8 and 12 weeks. While manufacturers usually recommend only one dose, the WSAVA guidelines recommend administration of two doses in puppies for best results. Revaccination in adult dogs is only recommended if they are at risk (frequent contact with other dogs) and is yearly.

 

Very importantly, I would NOT recommend waiting after all the full primovaccination course for socialisation. During that vaccination period, until 2-3 weeks after the final vaccine (which per guidelines should be given at 14-16 weeks), there will be a number of puppies that are not protected from disease. Waiting until 16-18 weeks old to socialise would be very detrimental and dangerous. The risks of puppies getting a vaccinal infectious disease is low if they are being socialised with humans, cats etc, and with dogs that are healthy and vaccinated (including puppy parties, which I’d start at least 2 weeks after the first vaccine injection is given, so at around 10 weeks old if I start vaccinating at 8 weeks). Places with like streams, rivers, lots of wildlife or rodents, or lots of unknown dogs or their faeces should be avoided until the puppy is 16-18 weeks old (2-3 weeks after final vaccines). The risk of getting leptospirosis and other diseases should then be low (unless in situations like local outbreak, crowded conditions etc where vaccines can be given every 2 weeks until 14-16 weeks). Any puppy younger than 16-18 weeks and becoming ill can have a disease against which we vaccinate and this should be explained to owners; owners should be told to seek veterinary attention straight away if the puppy becomes ill.

Finally I consider that vaccination against Borrelia burgdorferi and canine coronavirus are not recommended.

 

 

Q27: Could you tell me more about serotypes in Asia, more specific Indonesia. And is L4 available in this area? Dutch vet based in Jakarta.

C: Challenging question! I cannot find any data on serovars causing disease in dogs in Indonesia. I could find some data in humans:

–       A very good recent study mentions multiple serovars in South-East Asia: “There were negligible differences in predominate serogroup representation by geographic location, as evident from the various acute jaundice studies. The predominance of Hurstbridge serogroup, against a background of jaundiced disease, varies with previously documented findings from Indonesia. In an outbreak of jaundiced disease in South Sumatra (Indonesia), Australis, Grippotyphosa and Icterohaemorrhagiae were the most frequently recognized serogroups. Lastly, Bataviae was predominant among (febrile, nonmalarial) leptospirosis cases identified in Irian Jaya, Indonesia (as described in this article), whereas cases exhibiting febrile symptoms in Jakarta (1970–1971) were principally associated with the Pyrogenes serogroup.” (reference: Kanti Laras et al. The importance of leptospirosis in Southeast Asia. Am J Trop Med Hyg. 2002 Sep;67(3):278-86. Article accessible for free via the Pubmed website: hwww.ncbi.nlm.nih.gov/pubmed).

–       In one study on leptospirosis in humans, L. Bataviae was the predominant serovar on MAT serological testing (remember that MAT is only accurate in 50% cases or less to determine the infecting serovar) (reference: Markum HM. Renal Involvement in Leptospirosis at Dr. Cipto Mangunkusumo and Persahabatan Hospitals. Acta Med Indones. 2004 Jul-Sep;36(3):148-52. Article accessible for free via Pubmed).

–       In one study, the blood of 137 human patients with fever (urban residents of Semarang, Indonesia) was tested for leptospirosis with MAT and PCR. 13 patients were positive for leptospirosis. The most frequently identified serogroup by MAT was Bataviae (5 cases). The study also mentions that the Dr. Kariadi University Hospital admits ≈50 severe cases of human leptospirosis each year, but such cases were not included in the study because of the high clinical suspicion of leptospirosis on admission with jaundice, azotemia, and/or bleeding (reference: Gasem et al. Murine typhus and leptospirosis as causes of acute undifferentiated fever, Indonesia. Emerg Infect Dis. 2009 Jun;15(6):975-7. Article accessible for free via Pubmed).

–       In one study, leptospirosis was diagnosed in 28 out of 226 human patients with fever, which confirms that the bacteria is around, but the serovars involved were not mentioned (reference: Punjabi et al. Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia. Am J Trop Med Hyg. 2012 Jan;86(1):46-51. Article accessible for free via Pubmed).

–       The abstract of one study mentions that leptospirosis is endemic and mortality is high in affected humans in Semarang, Indonesia (reference: Wagenaar et al. Long pentraxin PTX3 is associated with mortality and disease severity in severe Leptospirosis. J Infect. 2009 Jun;58(6):425-32).

–       In one study, sixty patients with severe leptospirosis were assessed for pulmonary involvement. The cases were from Dr. Sardjito Hospital, Yogyakarta (reference: Budiono et al. Pulmonary involvement predicts mortality in severe leptospirosis patients. Acta Med Indones. 2009 Jan;41(1):11-4. Article accessible for free via Pubmed).

–       A case report reported a patient with leptospirosis caused by Leptospira borgpetersenii serovar Sejroe infection on Bali Island, Indonesia (reference: Sakamoto et al. A case of leptospirosis caused by Leptospira borgpetersenii serovar sejroe infected in Bali Island, Indonesia. Kansenshogaku Zasshi. 2005 Apr;79(4):294-8).

–       In a study on 403 human patients with fever presented to a hospital in Makassar, Indonesia, a diagnosis of leptospirosis was confirmed for 24 (68.6%) patients, but the abstract does not mention which serovars caused the infection (reference: Hatta et al. Introduction of a rapid dipstick assay for the detection of Leptospira-specific immunoglobulin m antibodies in the laboratory diagnosis of leptospirosis in a hospital in Makassar, Indonesia. Southeast Asian J Trop Med Public Health. 2000 Sep;31(3):515-20).

 

So, all these studies tell us that leptospirosis is endemic in Indonesia, with some serogroups similar to what we see in Europe and which we know can affect dogs (Icterohaemorrhagiae, Canicola, Australis, Grippotyphosa), but also important other serogroups (Bataviae and Hurstbridge seem of important concern). I don’t know if those other serogroups can affect dogs. I certainly would want to be tested for leptospirosis myself if I became ill while in Indonesia.

More general vaccination guidelines for Asia from the WSAVA can be found here: www.wsava.org/article/wsava-vaccination-guidelines-asian-study-are-now-ready-view. These guidelines are however vague about which serovars should be used for vaccination against leptospirosis.

 

Q28: What if we’re already using the Nobivac L4 vaccine?

C: Leptospirosis is unlikely to occur in your canine patients if you work in the UK. However leptospirosis remains a possibility in non-vaccinated dogs, in dogs having travelled outside Europe, and even vaccinated dogs may develop leptospirosis as no vaccine is 100% effective. There is also the risk of a future change in epidemiology and non-vaccinal serovars may become endemic in the UK in the future. Also Nobivac L4 has not been approved to reduce renal carriage by the serogroup Australis (including serovar bratislava), so although vaccinated dogs should be protected against developing disease from this serogroup, asymptomatic renal carriage cannot be excluded for this serogroup. Finally depending on where you work, other serogroups such as Pomona may be present in other European countries and may cause disease. So overall I would say that although leptospirosis is unlikely to occur in your vaccinated patients, it is worth keeping the disease in mind.

 

Q29: When vaccinating puppies, can the DHP be given separately to the Nobivac L4 for the second vaccine and the L4 given later after 4 weeks so puppies could get out earlier for socialisation and still be protected from parvovirus?

C: You could vaccinate earlier for DHP and later for leptospirosis. See question 25 for my recommendations about puppy vaccination.

 

Q30: Is there a case for human vaccination in triathlon athletes and sewage workers?

C: Maybe. I cannot really answer this question as it would depend on the frequency of the disease in a specific location in those groups of people. There are human vaccines against leptospirosis available in some countries, including France, China, Cuba and Russia. As in animals, the vaccines are relatively serovar-specific and protect for a relatively short period. Boosting at regular intervals is necessary to maintain a protective immunity (reference: Hartskeerl et al. Emergence, control and re-emerging leptospirosis: dynamics of infection in the changing world. Clin Microbiol Infect. 2011 Apr;17(4):494-501). I think concerns about vaccine safety have also been raised in humans.

 

Q31: I’m interested in information on leptosirosis occurence in PL. Only very few practitioners do additional tests, and the data in PL is very poor. Where can I find a literature about this?

C: Hi, I am assuming PL is Poland.

In a recent study published in 2005, blood samples were taken from 4319 cattle, 3004 pigs, 998 sheep, 104 goats, 130 dogs and 98 wild pigs (Sus scrofa) between 1996 and 2000. All the animals lived in the northern part of Poland, in an area of 4516 km2 near the city of Torun; none was vaccinated against leptospirosis. Serum samples were tested with the microscopic agglutination test (MAT) against 18 leptospiral antigens. 640 sera were found to be positive (7·4 per cent of the tested animals). Titres to leptospiral antigens were present in 21·5 per cent of the dogs. In dogs, serovar Sejroe was most common based on MAT testing (12·3 per cent), followed by Canicola (6·9 per cent). In wild pigs, the highest prevalence of titres was recorded with serovar Sejroe (6·1 per cent of infected animals), followed by Poi (5·1 per cent); in goats, serovar Bratislava (2·9 per cent); in domestic pigs, serovar Poi (1·3 per cent) followed by Zanoni (1·2 per cent); in cattle, serovar Sejroe (3·4 per cent) followed by Hardjo (1·4 per cent); and in sheep, serovar Australis (0·6 per cent) (reference: Krawczyk M. Serological evidence of leptospirosis in animals in northern Poland. Vet Rec. 2005 Jan 15;156(3):88-9). It should be remembered that MAT is only accurate in 50% of cases or less in determining the infecting serovar. I could not find any data on the incidence of disease in dogs in Poland, so I cannot tell how frequent clinical leptospirosis is.

 

 

Q33: What about the IFA serology test offered by Biobest? This is a test for pathogenic leptospires, not affected by vaccination. Faster turnaround than MAT but doesn’t give information on the serogroup.

C: The immunofluorescence antibody test (IFA) commercially available in the UK and offered by Biobest detects antibodies against the sheath antigen shared by pathogenic leptospires. It does indeed not allow determination of the infecting serovar. This test is reported to be less costly than the MAT and results can be obtained more rapidly.  However data on the test’s sensitivity and specificity in the field is not currently available.

In a small clinical trial including limited numbers of dogs (31 dogs in total), this test detected all non-vaccinated dogs challenged with Leptospira and none of the vaccinated dogs. Additional samples that had been tested by MAT were also tested. Of 23 samples reported positive by MAT, 10 were positive by IFA. The difference between the IFA and MAT results may be due to better specificity of the IFA, better sensitivity of the MAT or a proportion of the MAT positives being due to vaccination.

So overall I would say that this is a promising test for screening, but we don’t know enough about its sensitivity or specificity to recommend its use, and I am concerned in particular that results positive by MAT but negative by IFA have been reported; we don’t know if these cases had clinical leptospirosis. The IFA test is unlikely to be as sensitive as PCR. False-positives may also occur with nonspecific binding of the antibody. Any positive results with the IFA test should be confirmed with MAT or PCR.

References:

–         Burr P, Lunn K, Yam P. Current perspectives on canine leptospirosis. In Practice 2009;31:98-102.

–         Burr P, Yam P. Clinical research abstract: Detection of leptospira antibodies in dogs by immunofluorescence. Annual congress of the British Small Animal Veterinary Association 2010; p.412.

–         Harkin KR. Leptospirosis. In: Bonagura JD,Twedt DC, eds. Kirk’s Current veterinary Therapy XIV. Saunders Elsevier, St Louis, Missouri, 2009;1237-1240.

 

Q34: Is human disease also treated with doxycycline?

C: I am not sure if doxycycline is used in all cases, but I was once treated preventively with doxycycline myself (I got the flu shortly after being in contact with a dog with leptospirosis, so I was treated while test results were pending, which came back negative).

 

Q35: Can dogs be treated initially with amoxicillin-clavulanate injections, then amoxicillin-clavulanate orally for one week then doxycycline for two to three weeks?

C: Yes, this would be appropriate, although I would usually change to doxycycline as soon as the dog can tolerate oral medication. See questions 12 and 19 for more discussion about treatment and antibiotic doses.

 

Q36: Any views on IFA screening?

C: see question 33.

 

 

Q38: Can vaccine-induced immunity against leptospirosis be boosted by exposure to wild-type leptospires?

C: I don’t think that any studies have looked at this, but we know that some dogs become exposed to Leptospira species in nature and develop antibodies without becoming ill, so I would suspect that exposure to vaccinal serovars of Leptospira may increase immunity.

 

Q39: Is it OK to use the Nobivac L4 vaccine at the same time than the intranasal parainfluenza vaccine?

C: See question 25 for more advice on vaccination in puppies.

 

Q40: You said that 10% bleach kills leptospires. Do you mean final concentration or 1:10 dilution? Because there is no commercial solution of 10% bleach.

C: Hi, industrial bleach seems to be around 10% and can be bought (here on Amazon: http://www.amazon.co.uk/gp/product/B00915WEEK/ref=pd_lpo_sbs_dp_ss_1?pf_rd_p=479289247&pf_rd_s=lpo-top-stripe&pf_rd_t=201&pf_rd_i=024500906X&pf_rd_m=A3P5ROKL5A1OLE&pf_rd_r=1PKXXCHR4TNX5PT8DXAS).

One review article mentioned that 10% bleach could be used to treat outdoor areas where dogs urinate. A 1:1 dilution of 10% bleach with water could be used to inactivate urine collected via a urinary catheter. Iodine-based disinfectants, accelerated hydrogen peroxide and quaternary ammonium solutions are also effective (reference: Sykes et al., 2010 ACVIM Small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment and prevention. J Vet Intern Med 2011, 25:1-13).

 

Q41: For how long do vaccines protect from urinary shedding?

C: It depends on the vaccine. Only some vaccines have been proven to protect against renal carriage in dogs. For Nobivac L4:

–       Study 3 weeks after vaccination: in one study, dogs (a group of vaccinated dogs and a control group) were experimentally challenged 3 weeks after the second vaccination. The results demonstrated that Nobivac L4 vaccine induced sterile immunity against leptospiraemia and renal infection with strains of serogroups Canicola, Icterohaemorrhagiae and Grippotyphosa, and induced sterile immunity against leptospiraemia with a strain of serogroup Australis. This led to the claim that Nobivac L4 protects against renal carriage from Canicola, Icterohaemorrhagiae and Grippotyphosa serogroups. Nobivac L4 has not been approved to reduce renal carriage by the serogroup Australis (including serovar bratislava), so although vaccinated dogs should be protected against developing disease from this serogroup, asymptomatic renal carriage cannot be excluded (reference: Klaasen et al. A novel tetravalent Leptospira bacterin protects against infection and shedding following challenge in dogs. Vet Rec. 2013 Feb 16;172(7):181).

–       Study 12 months after vaccination: in one study, dogs (a group of vaccinated dogs and a control group) were experimentally challenged twelve months after the second vaccination. The vaccine was able to either prevent or significantly reduce infection following challenge with the strains of all four serogroups. The vaccine was also able to prevent or significantly reduce renal infection following Canicola and Icterohaemorrhagiae challenge, and there was a trend of reduction of renal infection with Australis (serovar bratislava). In the case of the Grippotyphosa study, challenge led to no detectable renal infection in any dog of the control group, so protection against renal carriage by this serogroup could not be assessed (reference: Klaasen et al. A new tetravalent canine leptospirosis vaccine provides at least 12 months immunity against infection. Vet Immunol Immunopathol. 2014 Mar 15;158(1-2):26-9).

 

Q42: If an adult dog has missed its leptospirosis booster, say by one year, does it then need a single dose to re-establish immunity, or does it need to start the course again?

C: As immunity probably doesn’t last much longer than a year (contrary to vaccination against parvovirosis, distemper or hepatitis), a dog having missed a booster would need two injections of leptospirosis vaccination again, at 2-4 weeks interval depending on the vaccine used.

 

Q43: what are the most common clinical signs of leptospirosis in cats?

C: The reported clinical cases were all cats with renal disease. Cats infected experimentally develop renal and hepatic inflammation.

 

Q44: How do you know how often the vaccine should be given if you can’t test for protection with serology?

C: Serum agglutinating antibodies, as measured by the MAT, usually only persist for 12-16 weeks after accination and are most of the time only present at a low level. However in experimental challenges, it was found that vaccinated dogs can be protected against leptospirosis even when they have no or very low detectable serum antibodies as measured by MAT. The duration of immunity for a vaccine is based on experimental studies: dogs vaccinated then challenged with pathogenic strains of Leptospira a while after vaccination, to see if they remain protected. I am aware of published studies demonstrating a one year duration of immunity for Nobivac Lepto 2 , Nobivac L4 (both MSD Animal Health) and Eurican L (Merial):

–       Nobivac Lepto 2: Klaasen et al. Duration of immunity in dogs vaccinated against leptospirosis with a bivalent inactivated vaccine. Vet Microbiol. 2003 Aug 29;95(1-2):121-32.

–       Nobivac L4: Klaasen et al. A new tetravalent canine leptospirosis vaccine provides at least 12 months immunity against infection. Vet Immunol Immunopathol. 2014 Mar 15;158(1-2):26-9.

–       Eurican L: Minke et al. Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine. Vet Microbiol. 2009 May 28;137(1-2):137-45.

 

C: and to all the people who thought the webinar was good: thank you very much!