Weil syndrome causing autoimmune haemolytic anaemia.

Weil syndrome is a fulminant form of leptospirosis, usually caused by spirochetal organism Leptospira interrogans. It is characterized by icterus, petechial rashes over the body, signs of renal failure and hepatic failure. Anaemia is a usual manifes- tation of Leptospira infection, but autoimmune haemolytic anaemia is rare. We report a patient with autoimmune haemolytic anaemia following Leptospira infection, which was responsive to high-dose steroid therapy.

Clinical and imaging manifestations of hemorrhagic pulmonary leptospirosis: a state-of-the-art review.

Leptospirosis, a spirochetal zoonosis, is frequently unrecognized due to its manifestation as an undifferentiated fever. It is an emerging infectious disease that has changed from an occupational disease of veterinarians, farmers, butchers, and other animal handlers to a cause of epidemics in poor and decayed urban communities in developing countries. Humans are infected when mucous membranes or abraded skin come into direct contact with the urine of infected animals, especially rats and dogs. Mortality from severe leptospirosis is high, even when optimal treatment is provided. The diagnosis of leptospirosis is based on clinical findings, history of direct or indirect exposure to infected animals in endemic areas, and positive serological tests. It should be considered in the differential diagnosis of patients with febrile illnesses associated with pneumonitis and respiratory failure, especially when hemoptysis is present. Severe pulmonary involvement in leptospirosis consists primarily of hemorrhagic pneumonitis. In advanced cases, adult respiratory distress syndrome and massive pulmonary hemorrhage may occur. Chest radiographs show bilateral alveolar infiltrates and/or resemble viral pneumonia, bronchopneumonia, tuberculosis, adult respiratory distress syndrome, and other causes of pulmonary hemorrhage such as Goodpasture syndrome. High-resolution computed tomography scans may show nodular infiltrates, areas of consolidation, ground-glass attenuation, and crazy-paving patterns. Bronchoalveolar lavage and autopsy studies have suggested that ground-glass opacities and air-space consolidations are secondary to pulmonary hemorrhage. Although not specific, the presence of these computed tomography findings in a febrile patient with an appropriate history should suggest a diagnosis of leptospirosis.

Severe course of rat bite-associated Weil's disease in a patient diagnosed with a new Leptospira-specific real-time quantitative LUX-PCR.

Leptospirosis is a zoonotic disease with global distribution, caused by spirochaetes of the genus Leptospira. Transmission of Leptospira interrogans serovar Icterohaemorrhagiae, the causative agent of Weil's disease, to humans usually results from exposure to the urine of infected, but mostly asymptomatic, rodents, either by direct contact or indirectly through contaminated soil or water. Although regarded as a re-emerging infectious disease, human leptospirosis is probably underdiagnosed due to its often unspecific clinical appearance and difficulties in culturing leptospires. Therefore, more rapid and specific diagnostic procedures are needed. Here we describe a novel real-time quantitative PCR system developed for the accurate and fast diagnosis of pathogenic Leptospira spp. Its usefulness in the management of a patient with rat bite-associated multiorgan failure is demonstrated.

Leptospirosis in French Historical Medical Literature: Weil's Disease or Kelsch's Disease?

Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few historical differential diagnoses were malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in "constrained settings." Achille Kelsch (1841-1911) synthesized available military data and epidemiological perspectives to define "epidemic jaundice" as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil's disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.

[Clinicomorphological characteristics of icterohemorrhagic leptospirosis].

Thirty three cases of death from icterohemorrhagic leptospirosis were clinically and morphologically analyzed. The disease is characterized by the affliction of two major target organs: the kidney and liver. Infectious-toxic shock underlies the pathogenesis of specific fetal complications of icterohemorrhagic leptospirosis. In the latter, acute renal-hepatic failure is always followed by the structural damage and dysfunction of other organs, which are less pronounced and, at the same time, presents multiple organ dysfunction.

Influence of leptospirosis on reproductive performance of sows in Brazil.

The purpose of this study was to investigate the association between seropositivity for the most frequent Leptospira serovars and reproductive losses in sows in Brazil. Serum samples from 351 sows from 18 herds (in the state of Rio de Janeiro, Brazil) with low reproductive efficiency were tested (microscopic agglutination) for antibodies against serovars of Leptospira. Antibodies were detected in serum samples of 66.1% of all sows, most frequently serovar icterohaemorrhagiae (43.1%), followed by pomona (18.1%) and tarassovi (9.9%). Seroreactivity to icterohaemorrhagiae and pomona were associated (P<0.05) with impaired reproductive performance (and substantial economic loss). Seroreactivity for pomona was associated (P<0.05) with stillborn piglets and mummified fetuses, whereas seroreactivity to icterohaemorrhagiae was associated (P<0.05) with the number of piglets born dead.

Highly Pathogenic Leptospira Found in Urban Brown Rats (Rattus norvegicus) in the Largest Cities of Sweden.

Leptospirosis is an emerging zoonosis of global concern; however, its contemporary occurrence in Sweden, a European country partly located north of the Arctic Circle, is poorly known. Four out of 30 brown rats, captured within urban districts in Sweden, were found to be positive for antibodies to Leptospira interrogans serovar Icterohaemorrhagiae. This serovar causes Weil's disease in humans, a severe infection with jaundice, renal failure, and hemorrhage. Our study is the first finding of this highly pathogenic serovar in Swedish rats since the 1930s.

A waterborne outbreak of leptospirosis among United States military personnel in Okinawa, Japan.

A waterborne outbreak of leptospirosis occurred among US military personnel during September 1987, on the island of Okinawa, Japan. Micro-agglutination titres for leptospiral antigen of greater than or equal to 200 were detected in hospitalized adult males averaging 22.5 years of age with symptoms compatible with leptospirosis. Epidemiological findings revealed two case clusters distinguished by time and place of exposure. The overall attack rates among recreational swimmers and combat skills training participants were 467/1000 (7/15) and 183/1000 (15/82), respectively. Swallowing of water differentiated individuals with laboratory-confirmed infection from those with no infection, while water immersion alone did not appear to result in leptospiral infection. Additionally, subnormal rainfall may have contributed to the risk of exposure associated with this outbreak.

Leptospirosis in Latin America.

Leptospirosis is a common disease in Latin America. Transmission to humans occurs by contact with water or soil contaminated with the urine of rodents, dogs, or livestock. Pathogenesis is still poorly understood, and bacterial toxin or virulence factors are probably responsible for many features of the disease. The anicteric form is the most frequent presentation, and its clinical picture resembles influenza or other acute febrile diseases. Icterohemorrhagic leptospirosis, or Weil's syndrome, represents the severe form of the disease. Its clinical picture is similar to bacterial sepsis and multiple organ involvement occurs, mainly in kidneys and lungs, and causes great morbidity and mortality. Death is often related to multiple organ failure and pulmonary hemorrhages. Diagnosis is based on serology or blood, cerebrospinal fluid and urine cultures in specific media. Treatment involves a combination of antibiotics and supportive measures.

Detection of Leptospiraceae by amplification of 16S ribosomal DNA.

The polymerase chain reaction (PCR) was developed to detect Leptospiraceae. Primers were used to amplify 1 631 base-pair (bp) 5'-region of 16S rDNA. Representative strains from the species, Leptospira interrogans sensu stricto, L. borgpetersenii, L. noguchii, L. santarosai, L. weilii, L. inadai, L. meyeri and the single member strain of Leptonema were amplified. In contrast, strains representing the saprophytic species. L. biflexa, L. wolbachii and L. parva were not amplified. There was no PCR product from 23 phylogenetically unrelated species of bacteria. As little as 10-1 pg of purified DNA and as few as 10-1 leptospires could be detected using the PCR analysis. Isolates of leptospires from clinical sources gave a positive PCR band, but those from surface waters did not.

Localization of the Leptospira interrogans metF gene on the CII secondary chromosome.

An open reading frame of 885 nucleotides was identified as the Leptospira interrogans metF gene. The deduced amino acid sequence (294 amino acids) showed similarities with Escherichia coli methylene tetrahydrofolate reductase (MetF or MTHFR) (33% identity) and with the N-terminal part of human MTHFR (33% identity). The L. interrogans metF gene complements an E. coli metF mutant to prototrophy, suggesting the functionality of the folate branch converging to form methionine. In addition, the L. interrogans MetF was found to be thermolabile. The metF gene belonged to the CII secondary chromosome, in contrast to the previously isolated metY and metX genes, which have been localized to the CI chromosome of Leptospira sp.

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.

The route of entry of leptospires into the kidney tubule.

To study the migration of Leptospira interrogans serotype pomona through the kidney, conventionally-reared mice aged 2 or 3 weeks were infected intraperitoneally with this organism. Within the first 4 days, the organisms migrated from the capillary lumina to the interstitial tissue and provoked an interstitial oedema. By the 10th day they were seen between the epithelial cells of the proximal convoluted tubules and by the 14th day many were located within tubular lumina. There was no evidence of viable leptospires within the cells of the proximal tubules, though occasionally structures resembling leptospiral fragments inside lysosomes were observed. At no stage during the study were glomerular lesions seen.

First isolation of Leptospira fainei serovar Hurstbridge from two human patients with Weil's syndrome.

Leptospira fainei serovar Hurstbridge is a recently discovered Leptospira species and so far it has only been cultured from animal sources. Based on positive serology and positive PCR for L. fainei among patients suspected of having leptospirosis, a role in human disease seems likely. This study describes two patients with Weil's disease from whom L. fainei was cultured. A local source of the infections was suspected, as these two patients resided in the same area of Denmark, were hospitalised approximately at the same time and had not been travelling recently. The Leptospira species was determined by serology, PCR and sequencing of bacterial DNA. One patient developed autoimmune hepatitis in the course of the L. fainei infection and was treated with both antibiotics and immunosuppression with good effect. The other patient had a self-limiting disease and did not receive any treatment.

Leptospira interrogans serovar Valbuzzi: a cause of severe pulmonary haemorrhages in the Andaman Islands.

Outbreaks of leptospirosis that present with predominant pulmonary signs and symptoms have been occurring in the Andaman Islands since the late 1980s. Before this, pulmonary haemorrhage had not been observed as a common complication of leptospirosis in India. During an outbreak on North Andaman in 1997, four leptospire isolates were obtained from blood of a fatal case and three other patients who recovered. These isolates were characterized using serological and molecular techniques. Cross-agglutination absorption tests and microscopic agglutination tests using mAbs were used for serological characterization. Genetic typing was done using DNA sequencing of PCR products. Serologically, the isolates were closely related to strain Valbuzzi serovar Valbuzzi of serogroup Grippotyphosa. The sequences of PCR products from these isolates were compared with those of 45 strains belonging to seven species. The isolates showed 97.5-100 % sequence similarity to reference strains belonging to Leptospira interrogans, indicating that the isolates belong to L. interrogans. Serogroups Icterohaemorrhagiae and Australis have been incriminated as the cause of pulmonary haemorrhage in China, Korea and Australia. The four isolates characterized in the present study were obtained from patients with similar symptoms. However, they belonged to serovar Valbuzzi of serogroup Grippotyphosa, indicating that serogroups other than Icterohaemorrhagiae and Australis can also cause pulmonary haemorrhage.

In vitro studies of haemolysis by Leptospira interrogans serovars pomona and ballum.

Washed and unwashed red blood cells (RBC) from young calves, adult cattle, hamsters and humans were incubated with Leptospira interrogans serovars pomona and ballum. Washed cells suspended in saline were always haemolysed while unwashed cells and those which were washed and resuspended in plasma were never haemolysed, despite the presence of large numbers of organisms within the culture supernatant. Pomona produced greater haemolysis of cattle and human RBC than did ballum, but with hamster RBC ballum produced greater haemolysis than did pomona. A group of 6- to 9-month-old cattle infected with pomona showed no signs of clinical disease and RBC taken from them before infection and during the development of antibodies to pomona were haemolysed by pomona only after the cells were washed. Plasma therefore appears to have a protective function. This in vitro protective function of plasma even extended to plasma from young seronegative calves.

Bovine leptospirosis: experimental serovar hardjo infection.

Almost the full range of clinical signs observed in pregnant cattle naturally infected with Leptospira interrogans serovar hardjo was observed in this experimental study in which 22 heifers were infected by intraplacentome inoculation with serovar hardjo strains. These features included abortion, mummification, stillbirth, premature and term birth of weak calves and full-term birth of live apparently healthy calves. Leptospires were demonstrated in all but three calves by culture and or immunofluorescence.

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.