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Human leptospirosis--a review of 50 cases.

Epidemiological and clinical aspects of 50 consecutive patients, 47 adults and three children, hospitalized between 1977 and 1987 for human leptospirosis, were reviewed. 45 (90%) of the patients were from rural regions. 32 (64%) cases occurred in individuals at occupational risk for the infection. 35 (70%) cases were registered in the warm season. The source of infection was known in 34 (68%) cases. Weil's disease was diagnosed in 31 (62%) patients, aseptic meningitis in 12 (24%) and acute unexplained fever in seven (14%). Haemodialysis was required for 11 (35%) patients with Weil's disease. Three (6%) patients died. Cause of death was massive gastrointestinal haemorrhage in two and renal failure in one. Leptospira icterohaemorrhagiae was responsible for 39 (78%) cases, Leptospira canicola for six (12%), Leptospira grippotyphosa for two (4%), and Leptospira australis, Leptospira ballum and Leptospira sejroe, for one case each. A muscle biopsy was performed in six patients and a renal biopsy in three. Focal necrotic muscular changes, with mild mononuclear infiltrate, were found. Pigmented casts in distal convoluted tubules, mild interstitial inflammatory infiltrate and mesangial enlargement of some glomeruli were observed in kidney biopsies. A good knowledge of the protean clinical manifestations of leptospirosis and an accurate laboratory study are required for a correct diagnosis.

Adolescent↗

[Severe leptospirosis. Description of a series of 10 cases].

Clinical aspects of 10 consecutive patients hospitalized for acute human leptospirosis, confirmed by serology using the microscopic agglutination test (MAT), between 1975 and 1988 in a 1000 beds Teaching Hospital are retrospectively analyzed. All of them were male, mean age of 55, presenting a suggestive epidemiological data to be at risk for Leptospira infection. Leptospira icterohaemorrhagiae was responsible for 8 cases and Leptospira canicola for 2. 7 patients were treated, after 3-4 days of admittance, with penicillin. 5 patients died. Cause of death was gastrointestinal haemorrhage in 3 and cardiogenic shock in 2. We discuss the clinical, biochemical, pathological and therapeutic aspects of the acute human leptospirosis.

Aged↗

A minireview of the pathogenesis of acute leptospirosis.

Hemorrhagic diathesis is one of the most striking manifestations in acute leptospirosis. Hemorrhages are seen in infections due to Leptospira icterohaemorrhagiae as well as in those caused by Leptospira pomona. Thrombocytopenia is a constant feature and its finding can be useful for the diagnosis. Attempts to demonstrate the presence of a toxin in leptospires were unsuccessful. A few years ago, a syndrome of disseminated intravascular coagulation was associated with the physiopathogenesis of experimental leptospirosis with L. icterohaemorrhagiae. More recently, this syndrome was identified in cases of human leptospirosis and in hamsters infected with L. pomona. It appears now that other spirochetal infections (borreliosis) have a similar pathogenesis. Nonetheless, many points are still unclear: the primary cause of disseminated intravascular coagulation is unknown, as well as the virulence factors of spirochetes. Some points favor the presence of a toxic factor in leptospires: vascular damage that occurs in the absence of leptospires in damaged areas and the fact that antibiotic therapy is ineffective unless treatment is initiated early in the disease.

Acute Disease↗

VIRULENCE-LINKED COLONIAL AND MORPHOLOGICAL VARIATION IN LEPTOSPIRA.

Faine, S. (University of Sydney, Sydney, Australia), and J. van der Hoeden. Virulence-linked colonial and morphological variation in Leptospira. J. Bacteriol. 88:1493-1496. 1964.-Large-colony typical hooked Leptospira icterohaemorrhagiae was virulent for hamsters and guinea pigs. On cultivation, it was gradually replaced by a serologically identical small-colony avirulent straight mutant. The hooked virulent form was selected in vivo.

Animals↗

Experimental immunization of hamsters with an EDTA extract of Leptospira interrogans, serovar icterohaemorrhagiae.

The EDTA extract was prepared from the Leptospira interrogans serovar icterohaemorrhagiae. When inoculated subcutaneously in hamsters it conferred protection from challenge with virulent leptospires with a low dose (10 micrograms/ml) and low agglutinating antibody (40). The protection of animals obtained by the EDTA extract opens up the perspective of its use as a component of a vaccine for the control of leptospirosis.

Agglutinins↗

A comparative investigation and identification of Leptospira interrogans serogroup icterohaemorrhagiae strains by monoclonal antibody and DNA fingerprint analyses.

The identification of Leptospira interrogans icterohaemorrhagiae strains from a number of Reference Laboratories were confirmed using monoclonal antibody (MoAb) and DNA restriction endonuclease (EcoR1) analyses. With a few exceptions, strain fidelity was demonstrated. Three clinical isolates and one isolate from a rat (Rattus norvegicus) were identified on DNA fragment patterns and found to be similar to the reference strains, icterohaemorrhagiae copenhageni, I. "icterohaemorrhagiae" Ictero I and I. icterohaemorrhagiae RGA.

Animals↗

Restriction endonuclease DNA analysis of Leptospira interrogans serovars icterohaemorrhagiae and hebdomadis.

Antigenic variants of Leptospira interrogans serovars copenhageni and hebdomadis were examined by bacterial restriction endonuclease DNA analysis with EcoRI, XhoI, SalI, BstEII, and HindIII as the digesting enzymes. The antigenic variants were stable cloned strains which had been cultivated in media containing homologous immune serum. One of the strains examined has been reported elsewhere (R. Yanagawa and J. Takashima, Infect. Immun. 10:1439-1442) as having an antigenic makeup which more closely resembles serovar kremastos than the serovar hebdomadis parent. The closely antigenically related but naturally occurring serovars icterhaemorrhagiae strain RGA and copenhageni strain M20 were examined in parallel. No differences could be shown between the hebdomadis parent and any of its mutants. Serovars copenhageni and icterohaemorrhagiae produced patterns which differed in the high-molecular-weight bands only. The Shibaura parent strain did not differ from copenhageni M20, but the Shibaura M1 strain differed from the other mutants and from icterohaemorrhagiae RGA in its high-molecular-weight bands.

DNA Restriction Enzymes↗

Pathology of acute Leptospira interrogans serotype icterohaemorrhagiae infection in the Syrian hamster.

The pathology of acute Leptospira interrogans serotype icterohaemorrhagiae infection in the Syrian hamster was investigated up to 7 days after infection using histology, electron microscopy and an indirect fluorescence test for leptospires. The disease was characterized by the presence of many leptospires in the tissues, jaundice, leukocytosis, haemorrhages, endothelial alteration and thrombotic glomerulopathy. The leptospires were present intravascularly, in the interstitium penetrating between liver cells and tubular epithelial cells and in the tubular lumina. The presence of leptospires was not necessarily associated with lesions. These findings support both pathogenetic mechanisms suggested in the literature, namely: the ability of leptospires to penetrate actively between cells with detachment of tight junctions, without obvious lesions to the cells, and an immune-mediated process with immune complex formation and binding and activation of complement resulting in leukocytosis, thrombotic glomerulopathy, endothelial alteration and haemorrhages.

Acute Disease↗

Identification of a 36-kDa fibronectin-binding protein expressed by a virulent variant of Leptospira interrogans serovar icterohaemorrhagiae.

We investigated the ability of a virulent strain of Leptospira interrogans serovar icterohaemorrhagiae, its isogenic avirulent variant and a saprophytic strain to bind fibronectin using alkaline phosphatase-labelled fibronectin. A single 36-kDa fibronectin-binding protein was expressed only by the virulent strain and was located in the outer sheath according to proteinase K treatment results. The interaction of this protein with fibronectin was specific and the region of fibronectin bound to this potential adhesin overlapped the gelatin-binding domain. The inability of a RGDS synthetic peptide to inhibit the binding of fibronectin indicated that the cell-binding domain was not involved in this interaction. Considering the wide distribution of fibronectin within a host and the diversity of mammals involved in the epidemiology of leptospirosis, its implication in the cell attachment process of virulent leptospires is coherent with the multiplicity of target cells.

Adhesins, Bacterial↗

EFFECTS OF CARBON DIOXIDE ON THE COLONIAL GROWTH OF PATHOGENIC LEPTOSPIRAE.

Yanagawa, R. (National Institute of Animal Health, Kodaira, Tokyo, Japan), T. Hiramune, and J. Fujita. Effects of carbon dioxide on the colonial growth of pathogenic leptospirae. J. Bacteriol. 85:875-880. 1963.-The growth of colonies of pathogenic leptospirae was examined in air of various CO(2) concentrations, ranging from air from which CO(2) was absorbed to air with 20% CO(2) added, and was compared with the growth of other microorganisms of the genera Mycoplasma, Brucella, Vibrio, Erysipelothrix, Staphylococcus, Micrococcus, Sarcina, Klebsiella, Salmonella, Escherichia, and Bacillus. The colonial growth of the 24 strains of pathogenic leptospirae examined was similar to that of other organisms in that the growth was negative in air from which naturally contained CO(2) had been absorbed, the growth tended to be inhibited in 5 to 20% CO(2) in proportion to the CO(2) concentration, and good colonial growth of leptospirae was obtained in a relatively narrow range of CO(2) concentration (from the normal amount in air to around 1%). The growth of some leptospirae was accelerated in 1% CO(2), but not that of the strains of Leptospira icterohaemorrhagiae, which required a lower range of CO(2), and of L. canicola. The CO(2) requirement of pathogenic leptospirae was similar, to some extent, to that of Mycoplasma mycoides, but was not so high as that of Brucella abortus. Incorporation of C(14)O(2) was demonstrated in leptospirae.

Animals↗

The detection of genetic variation in Leptospira interrogans serogroup ICTEROHAEMORRHAGIAE by ribosomal RNA gene restriction fragment patterns.

Deoxyribonucleic acid from Leptospira interrogans serogroup ICTEROHAEMORRHAGIAE reference strains together with clinical and animal isolates were cleaved with EcoRI, electrophoresed and transferred to nylon membranes. An Escherichia coli MRE 600, 16S + 23S ribosomal RNA template was used in the synthesis of a single strand biotin-labelled cDNA probe using a reverse transcriptase. Ribosomal RNA cistrons present in the DNA fragments of strains were located using the cDNA probe. Between 4 and 7 well defined ribosomal RNA restriction bands were detected for the leptospires studied that varied in size from 12.1 to 0.57 kb. The hybridisation patterns were distinctive and unique for the reference strains that allowed for their characterisation. Similar patterns were observed for I. budapest M 20, I. "icterohaemorrhagiae" Ictero I and the type strain, I. icterohaemorrhagiae RGA. Clinical isolates and a isolate from a rat were compared with reference strain DNA patterns and identified as being similar to I. copenhageni M 20, I. "icterohaemorrhagiae" Ictero I and I. icterohaemorrhagiae RGA. These results indicate that ribosomal DNA fingerprinting may be useful in the classification and molecular epidemiology of pathogenic leptospires.

DNA Probes↗

Leptospira interrogans serovar icterohaemorrhagiae seropositivity and the reproductive performance of sows.

The reproductive performance of 28 sows seropositive to Leptospira interrogans serovar icterohaemorrhagiae was compared with that of 87 Leptospira sp. seronegative dams belonging to the same herd. Sows were sampled during 1988 to 1993. During this period the herd was not submitted to any kind of intervention (antibiotic therapy, immunoprophylaxis or rodent control). Relative risks (RR) of return to heat, mummified fetuses, stillbirth, and weak newborn piglets for infected sows were assessed and the differences in means of total piglets born per litter, piglets born alive, piglets effectively housed, weaned piglets, stillbirths, mummified fetuses, weak newborn piglets, weight at birth of the piglets effectively housed, weight at 21 days of life and weight at weaning were evaluated. Seropositive dams had a greater risk of having weak newborn piglets (RR = 1.67, 1.02 < or = CI 95% < or = 2.72) and also of having more weak newborn piglets per litter (P = 0.01). Other variables examined were not different (P > 0.05).

Aging↗

Production and characterization of monoclonal antibodies to the EDTA extract of Leptospira interrogans, serovar icterohaemorrhagiae.

Monoclonal antibodies (MABs) were produced against an ethylenediaminetetraacetate (EDTA) extract of Leptospira interrogans serovar icterohaemorrhagiae being characterized by gel precipitation as IgM and IgG (IgG1 and IgG2b). The EDTA extract was detected as several bands by silver staining in SDS-PAGE. In the Western blot the bands around 20 KDa reacted with a monoclonal antibody, 47B4D6, and was oxidized by periodate and was not digested by pronase, suggesting that the determinant is of carbohydrate nature. Immunocytochemistry, using colloidal gold labeling, showed that an EDTA extract determinant recognized by monoclonal antibody 47B4D6, is localized under the outer envelope of serovar icterohaemorrhagiae. The MAB raised against the EDTA extract was not able to protect hamsters from lethal challenge with virulent homologous leptospires.

Animals↗

Prevalence of rodent and mongoose leptospirosis on the Island of Oahu.

Sporadic occurrences of human leptospirosis in recent years throughout the State of Hawaii have resulted in at least one death. Because of the apparent association of rodents and possibly mongooses with human leptospiral infections, a survey for leptospirosis was conducted among rodents as well as mongooses on Oahu. No such work had been recorded since a survey of rodents and mongooses for leptospirosis 31 years ago. In the current work, the prevalence of rodent and mongoose leptospirosis in the districts of Oahu was determined by the kidney-culture method. A serologic study of the rodents and mongooses subjected to kidney culturing was also conducted by use of the microscopic slide agglutination test. There were 1.2 times as many kidney culture results that were positive as serologic results. High prevalence of rodent leptospirosis were found where there was considerable rainfall or fresh surface water such as from streams. The overall leptospirosis prevalence for rodents was 23.4 percent, and for mongooses it was 23.0 percent. The Norway rat (Rattus norvegicus) had the highest infection rate, 33.3 percent, and the predominant (72.2 percent) organism in these infections was Leptospira icterohaemorrhagiae, which causes Weil's disease in man. Observations of rodent leptospirosis recorded 31 years ago were compared with results of the current study. The mongoose (Herpestes auropunctatus) is the preeminent carrier of Leptospira sejroe, a serotype that generally causes a mild form of leptospirosis in man.

Agglutination Tests↗

A serological survey of leptospirosis in Prince Edward Island swine herds and its association with infertility.

A serological survey was undertaken to determine the prevalence of leptospirosis, and to investigate associations between leptospiral antibody titers, and herd measures of reproduction. Production records and leptospirosis serology were analyzed for 25 slaughter hogs from each of eleven randomly sampled farrow-finish operations on Prince Edward Island. The effect of selected leptospiral serovars on nonproductive sow days per parity (NPSD/P) and the proportion of pigs born dead was evaluated. The four most common serovars to which antibodies were detected were Leptospira icterohaemorrhagiae, L. bratislava, L. autumnalis and L. pomona, with respective prevalences of 57.1%, 35.1%, 3.4% and 1.5% of PEI slaughter hogs. None of these serovars was associated with increased frequency of stillbirths (p greater than 0.05). However, farms with a higher prevalence of L. bratislava antibody titers tended to have more infertility, as measured by NPSD/P (r = 0.738, p = 0.036 with Bonferroni adjustment). Also, farms with L. pomona antibody titers had higher NPSD/P than farms without L. pomona antibody titers (p = 0.0008 with Bonferroni adjustment). There was no association between NPSD/P and antibodies to either L. autumnalis or L. icterohaemorrhagiae (p greater than 0.05).

Animals↗

Leptospirosis presenting as atypical pneumonia, respiratory failure and pyogenic meningitis.

A 20-year-old man who looked after a pack of hounds was admitted with a short history of headache, fever, haemoptysis and muscle cramps. Investigations showed type I respiratory failure with diffuse pneumonitis, pyogenic meningitis and raised liver enzymes. Leptospirosis was suspected and treated with the appropriate antibiotics leading to a full recovery. The diagnosis was confirmed by a titre of I/2560 to Leptospira icterohaemorrhagiae. The case illustrates an unusual presentation of this infection and argues for early antibiotic treatment.

Adult↗

Canine leptospirosis in Detroit.

Among 433 stray dogs in Detroit, Michigan, surveyed for leptospiral agglutinins, 164 (37.8%) had significant titers to 1 or more leptospiral serotypes; from 123 suburban stray dogs tested, 23 (18.7%) had significant titers. The use of 2-mercaptoethanol on positive serum samples was helpful in identifying acute from chronic phase titers. Cross-reaction patterns also were clarified by the use of 2-mercaptoethanol. Cultural isolation of leptospires from dog urine was unsuccessful unless the urine had a pH from 6.6 to 8.0. Oral administration of sodium bicarbonate to alkalinize dog's urine resulted in the isolation of leptospires from dogs usually voiding acidic urine. Leptospira icterohaemorrhagiae was the most common serotype in this dog population by serologic techniques and was the only one isolated in culture.

Administration, Oral↗

Leptospirosis in Rattus norvegicus and Rattus rattus in Israel.

Leptospires were isolated from 21.2% of Rattus norvegicus (the brown rat) and 9.9% of Rattus rattus trapped in a survey of urban and rural areas in Israel. Microagglutination antibodies were found in sera of 9.4 and 8.1% of these rats, respectively. The 191 strains isolated belonged to six serogroups: Leptospira icterohaemorrhagiae (169), L. bataviae (3), L. semeranga (1), L andamana (1) and L. ballum (1) from R. norvegicus and L. ballum (13) and L. hebdomadis (3) from R. rattus. No significant differences were found between the infection rate of mature male and female brown rats, but all six strains isolated from young animals were obtained from male rats. Two factors influence the rat of Leptospira infection among urban brown rats: the age of the animals and the area in which they are trapped. Adult brown rats trapped in a newly infected area showed a considerably higher level of contamination (61.8%) than those trapped in areas where the infection had persisted for many years (22.8%). Young rats showed a low degree of contamination in both the old foci (5.7%) and the new foci (2.2%). New and highly infected areas were found during this survey in Tel Aviv (Carmel market) and its neighboring cities of Holon, Ramat Gan and Givatayim.

Agglutination Tests↗