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LfhA, a novel factor H-binding protein of Leptospira interrogans.

The early phase of leptospiral infection is characterized by the presence of live organisms in the blood. Pathogenic Leptospira interrogans is resistant to the alternative pathway of complement mediated-killing, while nonpathogenic members of the genus are not. Consistent with that observation, only pathogenic leptospires bound factor H, a host fluid-phase regulator of the alternative complement pathway. Ligand affinity blot analyses revealed that pathogenic L. interrogans produces at least two factor H-binding proteins. Through screening of a lambda phage expression library, we identified one of these as the novel membrane protein LfhA. Ligand affinity assays and surface plasmon resonance analyses of recombinant LfhA revealed specific binding of both factor H and factor H-related protein 1. Serological examination of infected humans and horses demonstrated that LfhA is expressed by L. interrogans during mammalian infection. LfhA may therefore contribute to the resistance of pathogenic leptospires to complement-mediated killing during leptospiremic phases of the disease.

Animals↗

Lethal infection of C3H/HeJ and C3H/SCID mice with an isolate of Leptospira interrogans serovar copenhageni.

Leptospira interrogans serovar Copenhageni strain RJ16441, a blood isolate from humans with the severe pulmonary form of leptospirosis, has previously been shown to cause fatal pulmonary hemorrhage in guinea pigs and asymptomatic chronic renal tubular colonization with urinary shedding in rats. In this study, RJ16441 caused lethal infection of both C3H/HeJ and C3H/SCID mice, but no hemorrhagic phenomena were observed.

Animals↗

[Analysis of the forrmation and dynamics of the "outside the body" portion of a population of the causative agent in a natural focus of leptospirosis].

Field experiments with the use of radioisotope models have shown that urine containing leptospirae is regularly excreted in the same "infected spots" of the territory under study. For this reason, it is an increase in the frequency of Leptospira excretion in each "infected spot", rather than an increase in the number of such spots, which occurs in the course of the epizootic. To detect the "infected spots" on the experimental ground with the use of radioisotope models, the registration of such spots for 5-7 days is sufficient. The excretion of urine by animals in the "infected spots" has been shown to decrease the acidity of the soil, thus creating conditions favorable for the survival of leptospirae in the soil.

Animals↗

Antigens recognized by the human immune response to severe leptospirosis in Barbados.

Serum samples obtained from patients hospitalized in Barbados with severe leptospirosis were tested by the microscopic agglutination test (MAT), enzyme immunoassay (EIA) and immunoblotting with leptospires that had been isolated from these patients. While serum samples taken a few days after onset of symptoms often showed no apparent correlation between MAT and EIA, later sequential serum samples produced similar profiles in both tests during the course of infection. Immunoblotting sonicate from Leptospira interrogans serovars arborea, copenhageni and bim with patients' sera, revealed reactions with a number of bands that corresponded with outer envelope components. These components included lipopolysaccharide (LPS), flagella and other outer membrane proteins, in addition to a low-molecular-weight (MW) carbohydrate cross-reactive with members of the Leptospiraceae. IgM antibodies elicited in the first to second week after infection reacted mainly with LPS and the low-MW cross-reactive carbohydrate. Comparative analysis of isolates of the same serovar by sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting showed that while two serovar arborea isolates were identical, serovar bim isolates differed significantly from each other. This difference was also observed in comparative MAT testing.

Agglutination Tests↗

Low prevalence of antibodies against the zoonotic agents Brucella abortus, Leptospira spp., Streptococcus suis serotype II, hantavirus, and lymphocytic choriomeningitis virus among veterinarians and pig farmers in the southern part of The Netherlands.

Serum samples from 102 veterinarians and 191 pig farmers from the southern part of the Netherlands were investigated for antibodies against Brucella abortus, Leptospira spp, Streptococcus suis serotype II, Hantavirus (HV), and lymphocytic choriomeningitis virus (LCMV). All samples were collected in 1993 and stored until this study was performed. The prevalence of antibodies against B.abortus in veterinarians (4.5%) was significantly higher (P = 0.01) than in pig farmers (0%). None of the veterinarians (0%) and only one pig farmer (0.5%) had antibodies against Leptospira spp. Furthermore, significantly (P = 0.015) more veterinarians (6%) than pig farmers (1%) had antibody titres against muramidase-released protein (MRP),a protein of pathogenic S. suis serotype II strains. None of the veterinarians and a total of 3 (1.6%) pig farmers had antibody titres against HV. The prevalence of antibodies against LCMV tended to be higher in pig farmers (2.6%) than in veterinarians (0%) (P = 0.10). It can be concluded that the prevalence of antibodies against the investigated zoonotic agents in veterinarians and pig farmers is low.

Agriculture↗

A study of "white spotted kidneys" in cattle.

A study was performed at an abattoir in Australia, in an attempt to correlate focal chronic interstitial nephritis (FCIN) producing the so-called "white spotted kidney", with Leptospira spp. and other pathogens in cattle. Samples of kidneys, urine and blood were collected immediately after slaughter from 46 two-year-old heifers, and 72 cows and bulls with gross lesions consistent with FCIN. The same samples were also collected from nine heifers and 12 cows with no gross kidney lesions. Aqueous humour was also collected from the eye of 17 of the adult animals. The sera were processed by a microscopic agglutination test for leptospira antibodies, while all the other samples were cultured for Leptospira spp. and also processed for routine aerobic and anaerobic culture for other pathogens. Sub-samples from all the kidneys were fixed in 10% buffered formalin and processed histologically. Antibody titers of 1:400 or higher for Lepstospira borgpeterseni serovar hardjo were found in six adult animals with FCIN and in one adult animal with no gross kidney changes, while antibody titers of 1:400 to L. borgpeterseni serovar tarassovi were found in only one animal with FCIN. L. borgpeterseni serovar hardjo was isolated from the urine and kidney of one adult animal and from the urine of another adult animal, both with FCIN. No pathogens were isolated from any of the other samples. The histological lesions were consistent in most cases with FCIN. The results suggest that neither Leptospira spp. nor active infection by other bacteria are associated with the so-called "white spotted kidneys".

Abattoirs↗

Aseptic meningitis caused by Leptospira australis.

Meningeal involvement in leptospiral infection is quite common, usually mild and often overlooked. In contrast, cases of isolated involvement of the central nervous system, including aseptic meningitis, have been reported only rarely. A case of a patient with acute aseptic meningitis caused by Leptospira australis serovar bratislava is reported. This is believed to be the first report of aseptic meningitis due to Leptospira australis. This case indicates the need to consider human leptospirosis in the differential diagnosis of aseptic meningitis.

Adult↗

Seroepidemiology of Leptospira interrogans serovar hardjo in Colorado antelope and cattle.

A seroepidemiologic study was conducted to determine the prevalence of Leptospira interrogans serovar hardjo infection in Colorado cattle and antelope. Sera were tested by the microscopic agglutination test, using a standard battery of 12 antigens as well as 4 additional serovars of the Hebdomadis serogroup: hardjo, szwajizak, sejroe, and balcanica. Sera from 1,856 cattle and 544 antelope were tested. In both populations, the predominant serovar detected was hardjo; hardjo titers greater than or equal to 1:400 were found in 3.2% of the cattle and 3.6% of antelope. A positive correlation was found to exist between serologic evidence of infection in cattle and the presence of antelope. In counties with presumably infected antelope, 5.6% of cattle sera reacted to hardjo; in counties with uninfected antelope, 2.6% of cattle tested were seropositive for hardjo; where no antelope existed, titers of greater than or equal to 1:400 were not detected.

Animals↗

[Epizootiology of leptospirosis on industrial swine-breeding complexes].

Epizoovotiologic studies were carried out at two industrial pigbreeding complexes for 40,000 and 33,000 animals with a record of leptospirosis. The serologic examination of pigs made use of the microagglutination reaction in the investigation of a total of 3,793 blood samples by groups corresponded to the technology of raising introduced at such complexes--sows, growing animals, replacement animals, and pigs for fattening, along with the study of 20,914 blood samples taken from pigs in various regions of the country. The total number of positively reacting pigs accounted for 12.9 per cent. Highest was the percent of positively reacting sows and growing pigs--19.1 and 12.9, while the replacement animals showed 8.31. No positively reacting animals were found among the pigs for fattening. Highest titers were noted among sows--up to 1:12,800 (infectious), and lowest among growing pigs--up to 1:100 (postnatal). State are the substantial economic losses caused by abortions and stillborn piglets--11 and 23 per cent, resp., for the two complexes. The basic Leptospira type for the two complexes and for the country as a whole proved L. pomona. The main source of infection were the carrier pigs that excreted Leptospira organisms, and the infection at the industrial complexes came from the hybrid sows and boars imported from abroad for grading purposes. A biologically justified and economically expedient programme of immunoprophylaxis in the control of Leptospirosis was worked out, providing vaccination of replacement pigs and sows only, treatment taking place after impregnation.

Animals↗

Leptospira interrogans serotype hardjo outbreak in a Victorian dairy herd and associated infection in man.

Leptospirosis associated with probable L. hardjo infection was investigated in a dairy herd in a coastal district of Western Victoria. Thirty-six of 110 cows suffered leptospiruria and mastitis characterised by flaccid udders and abnormal milk. One of two media used enabled the isolation of the organism from infected guinea pigs inoculated with fresh urine. Microscopic agglutination titres to L. hardjo were elevated during the outbreak. There was an associated human infection.

Agglutinins↗

Penicillins, cephalosporins, and tetracyclines in treatment of hamsters with fatal leptospirosis.

A predictable 6- to 7-day course of a fatal Leptospira interrogans serovar bataviae infection in experimentally infected mature 110- to 150-g hamsters was used to evaluate the therapeutic efficacy of conventionally used and newer antibiotics. Active drugs were ampicillin, bacampicillin, cyclacillin, piperacillin, mezlocillin, doxycycline, chlortetracycline, cefotaxime, and moxalactam. Cephalexin, cefadroxil, cefamandole, and cefoperazone showed little or no activity in preliminary studies. In delayed treatment studies, all nine active drugs prevented death of hamsters even when treatment was delayed until 1 to 2.5 days before expected time of death. Leptospires in kidneys of surviving animals could be demonstrated in one or more hamsters treated with doxycycline, chlortetracycline, cyclacillin, and piperacillin, but in none of the animals treated with ampicillin, bacampicillin, mezlocillin, cefotaxime, and moxalactam. The potential usefulness of newer penicillins and cephalosporins, as well as ampicillin, chlortetracycline, and doxycycline, for treatment of severe leptospirosis is reported.

Animals↗

Leptospirosis in travelers.

Between 1987 and 1991 leptospirosis in 32 Dutch travelers was diagnosed. Infections were acquired predominantly in Thailand and other Southeast Asian countries. Contact with surface waters could be confirmed in all but one case. Fever, headache, and myalgia were the most common complaints. Signs included conjunctival injection and lymphadenopathy in 11 patients each, jaundice in 8, and nuchal rigidity in 3; renal function was impaired in 8. Leptospires were isolated from the blood or urine of nine patients. Thirty-one patients developed an antibody response. Classification of strains identified a variety of serogroups. Although only 14 patients received adequate treatment, all patients recovered completely. Since the number of patients with imported leptospirosis is increasing and the signs and symptoms of the disease are not specific, leptospirosis should be included in the differential diagnosis when a traveler returns from the Tropics with fever.

Asia, Southeastern↗

Control of immunologically crossreactive leptospiral infection by administration of lipopolysaccharides from a nonpathogenic strain of Leptospira biflexa.

In our previous paper (Matsuo, K., Isogai, E., and Araki, Y., Carbohydr. Res., 328: 517-524, 2000), antigenic polysaccharides obtained from the lipopolysaccharide (LPS) fraction of a nonpathogenic leptospira, Leptospira biflexa patoc Patoc I, are shown to be broadly crossreactable with most rabbit antisera elicited by immunization with various pathogenic leptospires. The result led us to test a protective effect of the same LPS in a hamster model system by heterologously challenging with a pathogenic leptospira, L. interrogans manilae UP-MMG. Firstly, a similarity in the antigenic epitopes of L. biflexa and L. interrogans was confirmed by the following assays. In the microscopic agglutination test (MAT), a hamster antiserum elicited by immunization with the L. biflexa-LPS preparation was shown to agglutinate cells of L. interrogans. Contrarily, in the enzyme-linked immunosorbent assay (ELISA), the L. biflexa-LPS preparation was shown to crossreact with a hamster antiserum elicited by immunization with whole cells of L. interrogans. These results suggest that the same or closely related antigens may be present on the cell surfaces of both L. biflexa patoc Patoc I and L. interrogans manilae UP-MMG. Furthermore, in a protective assay, the prior administration of a L. biflexa-LPS preparation resulted in raising a protective response in hamsters against challenge by L. interrogans without any side effect. The protective effect was strongly dependent on the dose amounts and/or administration times of L. biflexa-LPS. Thus, L. biflexa-LPS preparations can use as a potent vaccine against leptospirosis caused by various leptospires.

Agglutination Tests↗

Decision support models of leptospirosis in dairy herds.

Following the results of a survey which found that 61 per cent of dairy farmers felt that they needed more information about leptospirosis, and the strategies for its control and the costs and benefits involved, this paper describes the construction and preliminary results of two models of the disease intended to help explore the risks and financial implications of Leptospira interrogans serovar hardjo infection for dairy producers.

Animals↗