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.