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PubMed2005

Whole-genome analysis of Leptospira interrogans to identify potential vaccine candidates against leptospirosis.

Leptospirosis is an important global human and veterinary health problem. Humans can be infected by exposure to chronically infected animals and their environment. An important focus of the current leptospiral research is the identification of outer membrane proteins (OMPs). Due to their location, leptospiral OMPs are likely to be relevant in host-pathogen interactions, hence their potential ability to stimulate heterologous immunity. The existing whole-genome sequence of Leptospira interrogans serovar Copenhageni offers a unique opportunity to search for cell surface proteins. Predicted genes encoding potential surface proteins were amplified from genomic DNA by PCR methodology and cloned into an Escherichia coli expression system. The partially purified recombinant proteins were probed by Western blotting with sera from human patients diagnosed with leptospirosis. Sixteen proteins, out of a hundred tested, were recognized by antibodies present in human sera. Four of these proteins were conserved among eight serovars of L. interrogans and absent in the non-pathogenic Leptospira biflexa. These proteins might be useful for the diagnosis of the disease as well as potential vaccine candidates.

Antigens, Bacterial↗
PubMed1976

Co-antibodies in human leptospirosis.

Investigations concerning the co-antibodies formed in the course of human leptospirosis and the extractive antigens of leptospiras were reviewed. As a whole, the results concerning leptospira antigens point, next to antigens of serotype, to genus-specific and intertype antigens deeply seated in the cells. These cannot be identified by the MAL test, and therefore are not related to the co-agglutinins in human leptospirosis. The associations of co-antibodies in human leptospirotic sera were analyzed, using the MAL and CF tests performed with 20 pathogenic and water serotypes of leptospira. The results showed that in the course of human leptospirosis high titer co-antibodies are formed, both agglutinating and complement fixing, variably associated for one or more serotype antigens not belonging to the infecting strain. The various biological interpretations of the phenomenon were discussed and the hypothesis of antigenic changes of leptospira strains in vivo as well as in vitro was discussed, as a determining factor in the formation co-antibodies in leptospirosis.

Agglutinins↗
PubMed1995

The epidemiology of Leptospira interrogans serovar pomona in grower pig herds.

An epidemiological study on four farms showed that leptospiral infection became apparent in piglets from 12 weeks of age. The intensity of leptospiruria was greatest in the first 3-4 weeks of infection and from then on declined and became intermittent. Factors affecting the cultural and serological prevalence of infection of the piglets were found to be the standard of hygiene and variations in the titre of the dam. Dams with high titres gave better protection to their young than did those with low titres. The spread of infection within piggeries was encouraged by mixing infected with uninfected pigs, which resulted in epidemics within the pens. Transmission from infected to susceptible grower pigs continuously occurred in grower houses, with a constant proportion of pigs becoming infected each week.

Journal Article↗
PubMed1997

Invasion of Vero cells and induction of apoptosis in macrophages by pathogenic Leptospira interrogans are correlated with virulence.

Interactions of virulent Leptospira interrogans serovar icterohaemorrhagiae strain Verdun with Vero cells (African green monkey kidney fibroblasts) and a monocyte-macrophage-like cell line (J774A.1) were assayed by a double-fluorescence immunolabelling method. Infectivity profiles were investigated according to (i) the duration of contact between leptospires and eukaryotic cells and (ii) the number of in vitro passages after primary isolation from lethally infected guinea pigs. Comparative experiments were conducted with the corresponding high-passage avirulent variant and the saprophytic leptospire Leptospira biflexa Patoc I. In Vero cells, virulent leptospires were quickly internalized from 20 min postinfection, whereas avirulent and saprophytic strains remained extracellularly located. In addition, the virulent strain demonstrated an ability to actively invade the monocyte-macrophage-like J774A.1 cells during the early stages of contact and to induce programmed cell death, as shown by the detection of oligonucleosomes in a quantitative sandwich enzyme immunoassay. In both cellular systems, subsequent in vitro subcultures demonstrated a progressive decrease of the invasiveness, pointing out the necessity of using primocultures of Leptospira for virulence studies. Invasiveness of virulent leptospires was significantly inhibited with monodansylcadaverine, indicating that internalization was dependent on receptor-mediated endocytosis. Invasion of epithelial cells and induction of apoptosis in macrophages may be related to the pathogenicity of Leptospira, and both could contribute to its ability to survive in the host and to escape from the immune response.

Animals↗
PubMed2004

Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of Leptospira interrogans.

Leptospira interrogans causes a variety of clinical syndromes in animals and humans. Although much information has accumulated on the importance of leptospiral lipopolysaccharide in protective antibody responses, relatively little is known about proteins that participate in immune responses. Identification of those proteins induced only in the host is particularly difficult. Using a novel double-antibody screen designed to identify clones in a gene library of L. interrogans serovar Pomona expressing host-inducible proteins, we have characterized a gene (lk75.3) encoding a sphingomyelinase-like preprotein of 648 amino acids with cytotoxic activity for equine pulmonary endothelial cells and weak hemolytic activity for equine and rabbit erythrocytes. lk73.5 was found as a single gene copy in all serovars of L. interrogans but not in other Leptospira spp. except L. inadai. The open reading frame (ORF) for Lk73.5 is followed by another partially homologous sequence containing an ORF (sph-like 2) for a 28.7-kDa peptide. Lk73.5 and Sph-like 2 share 95.1 and 97.7% amino acid identity with putative sphingomyelinases Sph2 and Sph1 (N terminus) from L. interrogans serovar Lai (S.-X. Ren, G. Fu, X.-G. Jiangk, R. Zeng, Y.-G. Miao, H. Xu, Y.-X. Zhang, H. Xiong, G. Lu, L.-F. Lu, H.-Q. Jiang, J. Jia, Y.-F. Tu, J.-X. Jiang, W.-Y. Gu, Y.-Q. Zhang, Z. Cai, H.-H. Sheng, H.-F. Yin, Y. Zhang, G.-F. Zhu, M. Wank, H.-L. Huangk, Z. Qian, S.-Y. Wang, Wei Ma, Z.-J. Yao, Y. Shen, B.-Q. Qiang, Q.-C. Xia, X.-K. Guo, A. Danchinq, I. S. Girons, R. L. Somerville, Y.-M. Wen, M.-H. Shik, Z. Chen, J.-G. Xuk, and G.-P. Zhao, Nature 422:88-893, 2003). Substantial homologies to sphingomyelinases from other leptospiras and other bacteria are also present. Lk73.5 was not detected in leptospiras cultured at 30 or 37 degrees C. The recombinant protein reacted strongly with sera from recently infected mares but not with sera from horses vaccinated with commercial pentavalent bacterin. The host-inducible immunogenic Lk73.5 should have value in distinguishing vaccine from infection immune response.

Amino Acid Sequence↗
PubMed2002

Outbreak of leptospirosis among triathlon participants and community residents in Springfield, Illinois, 1998.

We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

Adult↗
PubMed2001

Leptospirosis.

Leptospirosis is a globally important zoonotic disease that affects humans on all continents, in both urban and rural contexts, and in temperate and tropical climes. Leptospirosis is a disease of the environment; transmission depends on interactions between humans and mammalian reservoir hosts. A variety of infectious diseases that present as undifferentiated febrile syndromes, such as malaria, dengue and influenza, as well as viral hemorrhagic fevers can mimic leptospirosis. The importance of pulmonary hemorrhage as a lethal complication of leptospirosis has become more widely recognized. In contrast to textbook dogma, population-based studies indicate that there is a poor correlation between infecting leptospiral strain and clinical expression of disease. Genetic transformation of a Leptospira sp. has now been reported, which should allow for detailed analysis of a variety of leptospiral genes. Publication of the whole Leptospira genome is eagerly awaited. Following recent reports of a new, highly effective conjugate typhoid vaccine, new efforts to find leptospirosis vaccines should include the manufacture and testing of conjugate leptospiral lipopolysaccharide vaccines. Recent advances, particularly in epidemiology, molecular genetics and pathogenesis, are placing leptospirosis at the cutting edge of biomedical science.

Bacterial Typing Techniques↗
PubMed1989

Measurement of IgG concentration in ovine fetal fluids: a useful diagnostic test.

The Veterinary Diagnostic Laboratory at Oregon State University received 172 aborted ovine fetuses during the 1985-1987 lambing seasons; from 120 of these, body fluids were evaluated for IgG levels. Fifty-two (43%) of the fetal fluids had immunoglobulin G (IgG) levels greater than 15 mg/dl. Forty-five (87%) of the fluids with elevated IgG levels were confirmed or presumed toxoplasma or chlamydia abortions. A mean fetal fluid IgG concentration of 111.5 +/- 78 mg/dl was found for the 26 toxoplasma abortions; for the 19 chlamydia abortions, a mean IgG concentration of 109 +/- 91 mg/dl was found. Antibody titers equal to or greater than 1:40 against Toxoplasma gondii were detected in 23 fetal fluids. Fetal fluid IgG concentration less than 15 mg/dl was found to be associated with bacterial organisms (i.e., Campylobacter sp.) as the confirmed or presumed cause of abortion. These results suggest that measurement of fetal fluid IgG concentration is a useful, supportive diagnostic test in determining the cause of ovine abortion, and should be included as a routine laboratory procedure for ovine abortion diagnosis.

Abortion, Veterinary↗
PubMedDate not supplied

[Leptospirosis--epidemic, clinical and diagnostic aspects].

Leptospirosis is a major public health problem throughout the world. We studied 22 cases of leptospirosis. They were hospitalised between 1999-2003. Men were more affected than women and those with rural origin prevailed, too. The direct infection was more often found in these cases. These patients presented a large spectrum of signs and symptoms attributable to this spirochetal pathogen. The etiology was dominated by L. pomona, L. canicola, L. wolffi. Leptospirosis presented with 3 syndromes: Weil's syndrome, atypical pneumonia syndrome and aseptic meningitis. The adequate treatment was with penicillin or ampicillin i.v.

Adolescent↗
PubMed1987

[Infectious endocarditis caused by rare germs. Review of the literature apropos of 2 cases].

The authors report two new cases of endocarditis secondary to exceptionnally encountered germs: one to Pasteurella pneumotropica, the other ascribed to Leptospira ictero-haemorragiae, on serologic criteria. Concerning these two cases, they propose to take a census of rare germs, from a detailed study of the literature. Among more than 5,000 cases of endocarditis published after 1944, are considered as rare germs those causing a disease in less than one p. cent of the cases. This purely "mathematical" definition enable to include 45 germs. A synthesis of all the cases reported attempts to demonstrate a few particular traits of these endocardites secondary to rare germs.

Adult↗
PubMed1994

[Leptospirosis in Pomurje and Slovenia].

In Pomurje leptospirosis is endemic. During the years 1964-1985 there were 407 leptospiral cases reported in Slovenia, 366 of which were in Pomurje. Inclusion in this study required indication of leptospirae with a fourfold increase of the titer of antibodies or the isolation of leptospirae from hemocultures. In Pomurje in this period 214 men (58.47%) and 152 women (41.53%) were infected. The average morbidity rate was 12.75/100,000 inhabitants. The highest rate was in the country of Lendava (23.14/100,000). Ten serotypes were confirmed: grippotyphosa in 122 (33.33%) of the patients, sejroe in 91 (24.86%), icterohaemorrhagie in 50 (13.66%), saxkoebing in 48 (13.11%), australis in 47 (12.84%), canicola and pomona in two cases, tarassovi and autumnalis in one patient. In one case, the serotype could not be differentiated. The disease occurs throughout the years. In contrast to Western Europe in Pomurje there exists a much larger percent of infected women and a high percentage among the elderly. Two patients have died (mortality rate is 0.55%). One of them succumbed on the 5th day of infection due to massive bleeding in the heart and other organs. The other died on the 12th day under the influence of a severe Weil's syndrome.

Female↗
PubMed1990

Zoonotic infections in Northern Ireland farmers.

Evidence of past zoonotic infection was investigated serologically in randomly selected Northern Ireland farmers. The percentage of farmers with antibody was: Brucella abortus (0.7), Leptospira interrogans serovars (8.1), Borrelia burgdorferi (14.3), Toxoplasma gondii (73.5), Coxiella burnetii (28.0), Chlamydia psittaci (11.1) and Hantavirus (1.2). The results show that Northern Ireland farmers have been exposed in the past to zoonotic infections. It is not known if these infections contributed to ill health in farmers but it is now time for the health of farm workers and their medical services to be reassessed.

Adult↗
PubMed2003

Evidence of herpesvirus infection in Woodland Caribou in Saskatchewan.

Sera were collected from 40 female and two male woodland caribou (Rangifer tarandus caribou) in Saskatchewan (Canada) from March 1992 to January 1995, inclusive. The samples were examined for antibodies against smooth Brucella spp., five serovars of Leptospira interrogans, bovine viral diarrhea virus, and bovine herpesvirus 1 (BHV-1). Twenty-two (52%) of 42 sera exhibited positive reactions to BHV-1 by a modified serum neutralization test, and the prevalence correlated positively with the age of the animals. No antibodies were detected against the other pathogens. This is the first reported evidence of herpesvirus infection in isolated populations of woodland caribou in western Canada.

Age Distribution↗
PubMed1978

Some infectious diseases of wild vervet monkeys (Cercopithecus aethiops pygerythrus) in South Africa.

Our surveys indicate that nearly all batches of vervet monkeys arriving at the National Institute for Virology from various areas of South Africa, are infected with foamy viruses and there is evidence that intra-urterine infection also occurs. Monkeys from certain areas of South Africa are apparently infected with the protozoal parasite Entopolypoides macaci in a sub-clinical state which becomes active when the monkeys are splenectomised. Serological studies indicate that infections with schistosomes, tick-bite fever (Rickettsia conori), chlamydsiae and occasionally by leptospirae, occur in monkeys in the Kruger National Park. Complement fixation tests for antibodies to R. mooseri and R. prowazeki were also sometimes positive; a finding of doubtful importance. There was a high percentage with positive antibody tests to chikungunya virus in a certain age group suggesting that there had been an outbreak of this disease in the Kruger Park in the late summer and autumn of 1976. This coincided with a human outbreak. Large numbers of vervet and baboon sera were tested for antibodies against SA 12 virus, a polyoma virus. A high percentage of baboons but only a small number of monkeys was found to be positive and it is concluded that SA 12 is probably a baboon virus which is occasionally transmitted to monkeys by contact. It is pointed out that these studies only indicate diseases from which monkeys recover and they do not indicate prevalence of severe disease causing grave illness or death.

Animal Population Groups↗