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Leptospira interrogans serovar hardjo was demonstrated in the vaginal discharges of 12 experimentally infected heifers for up to eight days after abortion or calving. Organisms were recovered from the oviducts of heifers examined at slaughter eight to 22 days after calving or 32 to 91 days after infection. They were also recovered from the uteri of four heifers eight to 22 days after calving.
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Blood samples were collected from 108 wild hogs (Sus scrofa) from the Great Smoky Mountains National Park (GSMNP), USA, February to July 1990. We found no antibodies for swine brucellosis, pseudorabies, bovine virus diarrhea virus or porcine rotavirus infection. Antibody titers to porcine parvovirus were found in 15 (14%) samples and antibody to one or more leptospiral serovars was found in 48 (44%) samples. Thirty-nine (89%) of the 44 positive samples reacted to all five leptospiral serovars tested.
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SUMMARYLeptospirosis, a widespread zoonotic disease caused by pathogenic Leptospira species, remains a major public health challenge, particularly in tropical and subtropical regions. Despite advances in understanding Leptospira biology and pathogenesis, effective disease control continues to be limited by the lack of rapid, early diagnostics, and broadly protective vaccines. This review comprehensively examines recent progress in deciphering Leptospira-host interactions, with emphasis on key virulence factors, immune-evasion mechanisms, and host immune responses that influence disease outcomes. Particular focus is placed on the molecular and cellular basis of adhesion, invasion, immune modulation, and persistent colonization. We further discuss the limitations of current vaccines and diagnostic approaches, and highlight how emerging technologies, including pan-genomics, proteomics, reverse vaccinology, immunoinformatics, and omics-based antigen discovery, are facilitating the development of next-generation vaccines and diagnostics. Finally, we outline major translational challenges and future perspectives for improving clinical management, surveillance, and prevention of leptospirosis. The concepts discussed in this review may also provide broader insights into vaccine and diagnostic development for other zoonotic bacterial infections.
A serologic survey was carried out on slum dwellers in the city of Rio de Janeiro. A total of 259 serum samples from male and female individuals of different age groups were tested for the presence of antileptospire antibodies by microagglutination. Prevalence data were analyzed in relation to the major risk factors present at the site, mainly represented by the presence of carrier animals and the occurrence of frequent floods. Of the samples tested, 25% reacted with antigens of different serogroups at titres ranging from 1:100 to 1:6400, with a predominance of titres less than or equal to 1:400; 35% of positive sera reacted with leptospirae of the Icterohaemorrhagiae serogroup. Reactions with Djasiman, Panama, Javanica, Canicola, Pyrogenes, Australis, Ballum, Sejroe, Bataviae, Grippotyphosa, Autumnalis and Cynopteri were also detected, though at lower frequencies. There was no statistically significant difference between sexes, but higher prevalence rates were found to be associated with increasing age. A focus of infection was characterized, in which social and economic factors contribute to the persistence of leptospirae by favoring the proliferation of the main reservoir.
Samples from 14 free-ranging pampas deer (Ozotoceros bezoarticus celer) were collected in 1995 and 1998, at Campos del Tuyú Wildlife Reserve, Buenos Aires, Argentina. Hematology, serum chemistries, minerals and metals, and fecal parasites were analyzed. In addition, fecal ova and parasites were evaluated seasonally during 1998-2000. Serology for infectious diseases included blue-tongue, brucellosis, bovine respiratory syncytial virus infection, bovine viral diarrhea/mucosal disease, infectious bovine rhinotracheitis, Johne's disease (paratuberculosis), foot and mouth disease (FMD), leptospirosis (eight serovars), epizootic hemorrhagic disease, and parainfluenza-3 (PI-3). Three (21%) pampas deer had antibodies to Leptospira spp. and six (43%) to PI-3 virus. Serologic results for all other infectious agents were negative. Domestic cattle (n = 27) included in this study for comparison had antibodies to Leptospira, infectious bovine rhinotracheitis virus, bovine viral diarrhea virus, and PI-3 virus (74-100% of tested animals) and one animal (4%) to Brucella sp. All cattle had antibodies to FMD virus attributable to vaccination. This study provides the first data on the health status of the southernmost sub-species of pampas deer.
Laboratory raised wild Norway rat males (Rattus norvegicus) were injected with leptospires of two serovars: icterohaemorrhagiae and grippotyphosa. The development of a carrier state was monitored serologically, culturally and histologically. Rats infected with icterohaemorrhagiae developed rapidly into a chronic carrier state and shed leptospires in the urine for the duration of the experiment (220 days). At the time of necropsy, histopathologic studies showed evidence of leptospiral infections in the lumen of proximal convoluted tubules of some kidneys. Rats infected with grippotyphosa shed organisms for 40 days after inoculation; thereafter, they apparently cleared the infection. No organisms were detected histologically nor by culture at the end of the experiment (220 days). There appears to be a specific host-parasite relationship in the Norway rat towards becoming chronic carriers when infected with serotype icterohaemorrhagiae but not with grippotyphosa.
Changes in lipid fractions were evaluated in young guinea pigs when infected with 1 ml of 7 day old live cultures of leptospira interrogans serovars australis, canicola and icterohaemorrhagiae. Statistically significant elevation in triglycerides, very low density lipoprotein and phospholipid and a significant reduction in high density lipoprotein (HDL) in all the groups was observed. Cholesterol and low density lipoprotein showed ascending trend in icterohaemorrhagiae group, whereas they were normal in other groups. The results suggest that increase in triglycerides, phospholipid and decrease in HDL in a suspected case of leptospirosis may be considered as markers.
A study was conducted to evaluate leptospirosis in brown rats (Rattus norvegicus), muskrats (Ondatra zibethicus) and mice (Mus musculus) in southeastern Larimer County, Colorado. Leptospira serotype icterohaemorrhagiae was isolated from fourteen of 143 feral brown rats, an infection rate of 9.8%. Serological evidence of infection with this stereotype was found in 66.4% of the rats. Serological evidence of L. serotype ballum infection was present in three of 17 muskrats. Leptospires were seen in histological sections of kidney tissue from two of 61 feral mice. No isolations were made from cultures and serology was not done on mice.
Wild brown rats (Rattus norvegicus) are frequently implicated in the carriage and spread of Leptospira spp. Wild brown rats (n = 259) were trapped from 11 UK farms and tested for Leptospira spp. using a number of diagnostic tests. The prevalence of leptospiral infection was low, but there was variation in the results obtained with the different diagnostic tests. Estimates of prevalence ranged between 0% by silver-staining of tissues, 1% by the microscopic agglutination test, 4% by the enzyme-linked immunosorbent assay, 4% by culture, and 8% by fluorescent antibody technique. In total, 37 (14%) rats were positive by at least one of the tests, which contrasts with the frequently reported prevalences of 50-70% for wild rats in the UK. Serovar bratislava was a prevalent as icterohaemorrhagiae, although it was present only on farms with larger rat populations.
From 10 days before the expected date of farrowing onwards, 97 sows infected by Mycoplasma hyopneumoniae and Treponema hyodysenteriae were given tiamulin daily at a dosage of 20 mg/kg bodyweight via the feed. Three days before farrowing the sows were washed with a disinfectant and transferred to an isolated farrowing house. The sucking piglets remained with their dams for five days, during which time the sows continued to receive the tiamulin-containing feed. The sucking piglets also received tiamulin daily at a dosage of 30 mg/kg bodyweight. At six days old the weaker piglets of the litter were returned to the original herd, together with their dams. A total of 574 piglets of about 1.5 kg bodyweight each were transferred to an isolated and previously disinfected pig farm and reared there. A total of 13.8 per cent of these pigs died by 50 days old. On the isolated farm, 10.9 per cent of the 829 second generation piglets born to the 101 first generation sows, died up to the age of 50 days. On the isolated farm about 2000 pigs were subjected to repeated clinical, pathological and laboratory examinations for M hyopneumoniae, T hyodysenteriae, Aujeszky's disease virus and Leptospira species during the three year period of study. No evidence of infection with any of these agents was found in the 2000 pigs of the isolation herd, although the original sow herd had been latently infected by these pathogens. No maternally derived antibodies against these pathogens were detectable in sera of three-day-old sucking piglets of the second and third generations.
An improved method of preparing bovine urine samples was developed for the rapid, specific, and sensitive detection of Leptospira interrogans serovar hardjo (subtype hardjobovis) DNA by the polymerase chain reaction (PCR). A total of 100 leptospire-free cows, 4 experimentally infected cows, and 2 negative control cows were used. PCR results were improved by (i) using 10-ml urine samples instead of 1-ml samples, (ii) adding 10(7) to 10(8) Leptospira biflexa serovar patoc cells as a carrier to each treated sample, (iii) preventing the loss of pelleted leptospires, and (iv) minimizing the presence of PCR-inhibiting factors in the samples. The preparation method enabled us to use the PCR to reproducibly detect as few as 5 to 10 leptospires per ml of urine without the need for dot blot hybridization. In addition, we were able to estimate the number of leptospires shed by experimentally infected cows.
PURPOSE: To define uveitis associated with leptospirosis in a clinical setting. METHODS: We present the clinical features of 73 consecutive cases of uveitis linked clinically to an outbreak of systemic leptospirosis in patients with antibodies to Leptospira species who were examined from January to September 1994. RESULTS: In 73 patients, the pattern of ocular involvement was unilateral in 35 and bilateral in 38. Panuveitis was seen in 106 eyes (95.5%), retinal periphlebitis in 57 eyes (51.4%), and hypopyon in 14 eyes (12.6%). Anterior uveitis alone without hypopyon was observed in three eyes (2.7%), whereas vitreous inflammatory reaction alone was seen in two eyes (1.8%). Sixty of 73 patients (82.2%) or 91 of 111 eyes (82.0%) were followed up for 8 months. Final visual acuity was 6/6 (20/20) in 47 eyes (52%) and improved during treatment, although not up to 6/6, in 15 eyes (16%). Twenty-eight eyes (31%) maintained same vision, and one eye showed deterioration of vision. CONCLUSION: Uveitis associated with leptospirosis may manifest as unilateral or bilateral uveitis, anterior uveitis, or panuveitis. The prognosis is generally good in this entity, even when the inflammation is severe. Awareness of this disease in endemic areas is important in order to differentiate it from other uveitic entities, especially in young male patients in whom other immunologic uveitides are also common.
OBJECTIVE: To evaluate the effect of vaccination against leptospirosis on frequency and days to recurrence of uveitis and progression of disease in horses with equine recurrent uveitis (ERU). ANIMALS: Forty-one horses with ERU. PROCEDURE: Horses were randomly assigned to experimental (vaccinated) or control groups. Vaccine containing six serovars of Leptospira or placebo was administered, an ophthalmic examination performed and blood samples drawn on days 0, 28, 180 and 365. Antibody titers were measured against each serovar. Recurrence of uveitis was verified by ophthalmic examination. Results of the initial and final ophthalmic examinations were compared and progression of disease defined as an increase in extent of synechiae, or development of new or progression of an existing cataract. RESULTS: Vaccination increased the average geometric mean serum antibody titer from 225 on day 0, to 4077 and 593 on days 28 and 180, respectively. After the second vaccination, days to first recurrence was significantly longer (median 126 days; range 24-231 days) when compared with controls (median 86 days; range 14-192 days, P=0.04). Recurrence of ERU was observed among 7/20 (35%) vaccinated horses and 12/21 (57%) controls; however, this difference was not statistically significant (P=0.061, OR 0.25, 95% CI 0.06, 1.07). More horses in the experimental group 13/20 (65%) experienced progression of disease when compared with controls 12/21(57%); however, this difference was statistically nonsignificant (P=0.35). CONCLUSIONS: Vaccine significantly increased days to recurrence, but failed to slow the progression of disease. These data do not support the use of vaccination against leptospirosis as adjunct therapy for the routine treatment of horses with ERU.
Leptospira interrogans serovars hardjo and szwajizak were isolated from the milk of experimentally infected cows only when using bovine albumin polysorbate-80 solid medium. Semisolid media, with and without the addition of 5-fluorouracil, and hamster inoculations were also used in the isolation attempts. These cultural isolation methods were also compared using cows' urine. Semisolid medium with 5-fluorouracil proved to be the most successful. However, the other methods were satisfactory, with solid medium having the lowest percentage of cultural isolations.