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).