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Leptospirosis is a zoonotic disease of worldwide distribution caused by infection with Leptospira genus bacteria, a pathogenic spirochaete. We present the case of a 29-year-old man admitted to our hospital with fever and multiorgan failure. He provided poor information about his symptoms. No recent travel or occupational history was reported and his clinical presentation did not suggest any infectious foci. His relatives later disclosed that he had been homeless for 3 weeks in the context of behavioural changes, obtaining foodstuff from waste containers and water from rain puddles. In the setting of this epidemiology, his presentation of fever, jaundice, acute renal injury and thrombocytopaenia suggested leptospirosis. Prompt empirical antimicrobial coverage was started, alongside organ support therapy. The diagnosis was later confirmed through microscopical and molecular methods. The patient made a full recovery. Leptospirosis should be considered early in the diagnostic work-up of any patient with acute febrile illness with multiorgan system involvement, with the identification of risk factors being essential to treat early in development of the disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There were few reports in the literature of Weil's disease with multiple organ failures, especially in children living in dengue endemic areas., Case Presentation: A 12-year-old child was admitted to Tangerang district hospital with a provisional diagnosis of dengue infection. On the third day of hospitalization, dengue diagnostic tests were negative. As fever still remained and was followed by jaundice, decreasing hemoglobin, increasing bilirubin with abnormal value of liver enzymes; other causes of disease were investigated. Leptospirosis was confirmed by rapid IgM test (SD(®)) for leptospira; and micro-agglutination test which indicated Leptospira serogroup bataviae infection. The patient developed Weil's disease during the course of illness. Renal function was back to normal on the 21st day of hospitalization, while hemoglobin and bilirubin returned to normal three weeks after discharged., Conclusions: Our report highlights the importance of considering leptospirosis as a differential diagnosis in children with acute febrile illness; even when the signs and symptoms for the more common diagnoses such as dengue or typhoid fever were pathognomonic. A normal leukocyte count with neutrophilia and negative dengue NS1, dengue IgM, and Salmonella typhi IgM on admission should raise suspicion of leptospirosis, and prompt diagnostic assays for leptospirosis should be conducted.

The aim of this study is to investigate the changes in clinical pattern and therapeutic measures in leptospirosis-associated acute kidney injury; a retrospective study with 318 patients in Brazil. Patients were divided according to the time of admission: 1985-1996 (group I) and 1997-2010 (group II). Patients were younger in group I (36 ± 13 versus 41 ± 16 years, P = 0.005) and the numbers of oliguria increased (21% versus 41% in group II, P = 0.014). Higher frequency of lung manifestations was observed in group II (P < 0.0001). Although increased severity, there was a significant reduction in mortality (20% in group I versus 12% in group II, P = 0.03). Mortality was associated with advanced age, low diastolic blood pressure, oliguria, arrhythmia, and peritoneal dialysis, besides a trend to better mortality with penicillin administration. Leptospirosis is occurring in an older population, with a higher number of oliguria and lung manifestations. However, mortality is decreasing and can be the result of changes in treatment.

We report a case of Weil's disease manifesting elevation of plasma D-dimer in the acute phase. Later, in the convalescent phase after treatment, the plasma levels of D-dimer returned to normal. Plasma D-dimer can be used as a marker of fibrin formation and degradation. Based on our observations, we conjecture that fibrin formation and fibrinolysis may occur in the acute phase of Weil's disease.

A 51-year-old man became jaundiced, after experiencing flu-like symptoms for a week. On admission anaemia, thrombocytopenia, and hepatic and renal function disorders were present. One month previously he had had sinusitis. Thrombotic thrombocytopenic purpura (TTP)/haemolitic-uraemic syndrome (HUS) was suspected, but the thrombocyte count rose spontaneously. The leukocytosis indicated an infectious cause of the symptoms and the jaundice appeared to originate from intrahepatic cholestasis. All symptoms could be traced to leptospirosis icterohaemorrhagica (known as 'Weil's disease'). The source was possibly the patient's fishpond. He recovered spontaneously and was also treated with antibiotics. Leptospirosis, a multi-organ disease is seen ever more infrequently as an occupational disease in stock farmers and increasingly frequently in people whose hobbies involved animals.

Massive hemoptysis in patients with severe leptospirosis is often resistant to conventional therapies and can rapidly become fatal. Desmopressin is a fast-acting blood-saving agent used in various hereditary and acquired clotting disorders. We used desmopressin infusions to treat massive pulmonary hemorrhage in six leptospirosis patients with respiratory failure, shock, and multiple organ dysfunction. Hemoptysis ceased rapidly in every case, and five patients finally recovered. Two additional patients with less severe hemoptysis were also successfully treated.

Between March 1996 and September 1997, 15 farms located in Galicia (NW Spain) and experiencing suboptimal reproductive efficiency were visited and blood samples were obtained from all the lactating cows (n=442). Additionally, 1060 samples were obtained monthly from a cohort of 219 lactating cows belonging to nine of the farms between March 1996 and April 1997. All the samples were tested by microscopic agglutination (MAT) using live antigens representing the following Leptospira interrogans serogroups: Australis, Autumnalis, Ballum, Canicola, Grippotyphosa, Icterohaemorrhagiae, Louisiana, Pomona, Sejroe, Shermani and Tarassovi. Eighty-one of the 442 cows were positive against one or more serogroups (P=18.33%). Serologically, L. bratislava and L. grippotyphosa were detected as the most prevalent serovars (P=7.92 and 7.69%, respectively) and as the serovars against which the probability of seroconversion was highest (P=0.27 and 0.25, for a 12-month period, respectively) among those studied. The proportional hazards regression method was used for evaluating the seasonal trend of seroconversions against these two serovars. The risk of seroconversion against L. grippotyphosa was significantly higher during spring. The risk of seroconversion against L. bratislava did not differ significantly among seasons. Our results suggest that infections by L. bratislava did not follow, among the study animals and during the study period, the pattern typically described for non-adapted serovars, pointing out the possibility that some strains of this serovar could behave as adapted serovars.

Leptospirosis is a zoonosis caused by Leptospira interrogans. This disease is diagnosed by quantification of specific immunoglobulins in serum by the microagglutination test (MAT). The aims of this research were: a) to compare the protein profiles of 3 clinical isolates of bovine leptospirosis with the reference strain used for the MAT, and b) to identify the immunodomain antigens of the regional isolates through PAGE and immunoblotting techniques of bovine sera from infected, vaccinated and MAT-negative animals. Coomassie-blue stained gels revealed extensive protein similarities between pathogenic and reference strain. Most infected (8/10) and vaccinated animal sera (4/7) showed by immunoblotting a similar reactivity against the proteins from pathogenic leptospires, with a strong band of 25-30 kDa which was not detected in the reference strain. The lack of correlation between MAT and immunoblotting techniques for infected animals could be due either to the infection stage at which the diagnosis was made or to the immunoglobulin isotype involved in the response. Results obtained would confirm the antigenic differences between the 3 isolates and the reference strain.

A competitive enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody (M898) was developed for detection of bovine antibodies to Leptospira interrogans serovar pomona. This assay was evaluated using field sera (n = 190) with serovar pomona microscopic agglutination test (MAT) titers of > or =100 as the positive population (group A); field sera (n = 1,445) which were negative in the MAT (1:100 dilution) for serovar pomona (group B); and sera (from a specific-pathogen-free cattle herd [n = 210]) which were negative in the MAT (1:100 dilution) for serovars canicola, copenhageni, grippotyphosa, hardjo, pomona, and sejroe (group C). At the cutoff point recommended by receiver operating characteristic (ROC) curve analysis of the combined ELISA results of serum groups A, B, and C, the sensitivity and specificity values were 93.7 and 96.3%, respectively. The value for the area under this ROC curve was 0.977, indicating a high level of accuracy for the ELISA. Similar results were obtained from the analysis of the combined results of serum groups A and B and from the analysis of the combined results of serum groups A and C.

Blood samples from 46 patients with leptospirosis were analyzed on a Cobas Vega (ABX, France) device over the course of disease. Hemoglobin content, erythrocyte count, mean volume of erythrocytes, mean content and mean concentration of hemoglobin in an erythrocyte, anisocytosis index, reticulocyte count, and content of free hemoglobin (FH) were analyzed. Anemia (normocytic normochromic hyperregeneratory) is a typical manifestation of leptospirosis during the second week of disease. The leading pathogenetic mechanism of anemia associated with leptospirosis is erythrocyte hemolysis, whose intensity during the acute period depends on the severity of intoxication and extracorporeal methods of detoxication. Persistence of anemia during convalescent period is due to involvement of the kidneys (nephrotic nephritis).

The aim of the study was to look into the epidemiology of serodiagnosed cases of leptospirosis at the University Hospital and compare two commercial ELISA Assays to the Microscopic Agglutination Test (MAT). Demographic data for all serodiagnosed cases for the years 1991-1997 were collected. From this data, 104 sera (n = 104) were selected as samples for comparative evaluation of the commercial ELISAs (INDX Dip-S-Ticks and PanBio ELISA) to the MAT test. Thirty two (n = 32) negative control sera were selected from serodiagnosed cases of other differential diagnosis of leptospira infection. The MAT test is a standard test that detects agglutination antibodies to leptospira biflexa, while the INDX Dip-S-Ticks is an ELISA dot test assaying for total anti-leptospira antibodies. The PanBio ELISA is a colorometric assay in test well strips to detect anti-leptospira IgM. The sensitivity, specificity, and efficiency of tests were calculated at a MAT cut-off value of 1:320. Demographic data showed that leptospirosis peaks during March-May and Aug-Nov coinciding with the inter-monsoon period with more men being infected than women and more adults than children. The sensitivity, specificity, and efficiency of test for the INDX Dip-S-Ticks were 83.3%, 93.8% and 87.5% while the values for the PanBio ELISA were 54.2%, 96.9% and 71.3%. The suboptimal PanBio result could be related to the blocking effect of high IgG titres or could be related to the diagnostic MAT cut-off values used in this study. The data hence reflects a pattern of transmission that is related to "wet" occupational risk factors. The commercial assays evaluated, are easier to perform but interpretation of results should be based on level of endemicity. The INDX Dip-S-Ticks allows this flexibility and is a practical alternative to the MAT test.

Leptospirosis is an acute generalized infectious disease caused by a spirochete of the genus Leptospira. Humans become infected by direct contact with the animal reservoir or indirectly through standing water or contaminated wet areas; once the leptospira has entered the body through the mucosa or eroded skin, it is spread by blood circulation. It can cause hepatic, renal and muscular disorders, as well as meningeal inflammation. We report the case of a patient admitted to the ICU for an infectious process produced by leptospira. Complications are described and identified as nursing problems and/or diagnoses. Following the NANDA nomenclature, the diagnoses were: Tissue-perfusion disturbance. Deterioration of gas exchange. Deterioration of verbal communication. Nutritional disorder. These categories enabled specific nursing interventions to be planned for the patient's care. The patient died of multiple organ failure in spite of conventional care and treatment.

Acute hepatic insufficiency is the main link in the pathological process in leptospirosis determining the degree of severity of the condition and level of bodily compensatory potentialities. Pathogenetically, hepatic insufficiency runs its course through the following three stages: compensated, sub-compensated, and decompensated characterized by different levels of functional (excretory-biliary, protein-synthetizing, hemostatic, detoxicating) inadequacy.

The prevalence and risk factors associated with leptospirosis were studied in veterinary students in Zaragoza. Sera were collected at the beginning and end of the academic year 1994 to 1995 and were tested by ELISA against a pool of Leptospira interrogans serovars bratislava, canicola, grippotyphosa, hardjo, icterohaemorrhagiae and pomona antigens. At the beginning of the study the prevalence was 8.14 per cent and at the end it was 11.4 per cent. The incidence of the disease during the study was 0.0394. Risk factors associated with leptospirosis included: taking the course specialising in food inspection and technology, on-farm work, contact with pets in general, and particularly carnivores, and contact with animal traders. The symptoms associated with the disease were myalgia and fever, and the treatment of the symptoms provided some protection.

Twelve cases of leptospirosis followed by the Infectious Diseases Clinic of the Cukurova University Medical School, Adana, Turkey, between January 1994 and November 1995 are reported. Included are their clinical manifestation, laboratory findings and serotype. Nine men and three women with an average age of 40.4 years were studied. Symptoms, clinical manifestations, laboratory findings and treatment of the disease are evaluated. All of the patients had fever and chills and the following symptoms: nausea and vomiting (91.6%), lower back pain and myalgia (58.3%), headache (50%), epistaxis (16.6%) and confusion (25%). The predominant clinical findings were jaundice (91.6%), hepatomegaly (41.6%), dyspnea (25%), conjunctival suffusion (33%), and nuchal rigidity (33%). Diagnosis was based on dark-field examination of the blood, cerebrospinal fluid and urine specimens. Also, microscopic agglutination tests (MAT) were carried out for serodiagnosis. MAT showed L. interrogans serovar icterohaemorrhagiae in 11 cases and L. interrogans serovar grippomosocova in one case. There was cross reaction with L. biflexa patoc in all cases. Agglutinations were tested in the same specimens twice and confirmed in the Microbiology Laboratory of the Etlik Veterinary Research Institute in Ankara. All cases were treated with penicillin and doxycycline. In the end; 83.3% of the patients were cured and 16.6% died due to hepatorenal failure.

Morphologic studies were made on the brain tissue and internal organs of those deceased (n = 75) who had died of leptospirosis icterohemorrhagica during different periods of the condition, with the results obtained being compared to clinical and laboratory findings. It has been shown that realization of the pathogenic potential of the disease-producing germ is exercised both through direct generalized injury to the endothelium of microvessels, parenchymal cells (predominantly those of the liver and kidneys) by toxic substances of Leptospira and (to a larger degree) through disorders of hemostasis presented as thrombosis of vessels of the microcirculatory bed with subsequent development of hemorrhagic manifestations and alterative changes of hypoxic genesis in vital organs. Early haemocoagulatory disorders are characterized by marked and stable hypocoagulation, with direction of the processes of fibrin formation and fibrinolysis being different, which fact is consistent with diversity of structural formations originating from fibrin in the microcirculatory bed of the deceased. Prophylaxis of grave pathologic changes in the organism leading to lethal outcome consists in correction of hemostatic disorders during early phases of the disease course, which is to be pathogenetically substantiated and situational one because of the problem posed by verification of stages of that syndrome of disseminated intravascular coagulation in patients with grave course of leptospirosis icterohemorrhagica.

Samples of cervico-vaginal mucus from 163 bulling cows (group 1) and post calving discharges from 59 newly calved cows (group 2) in five dairy herds naturally infected with Leptospira interrogans serovar hardjo were examined for the presence of antigen and IgG and IgA antibodies by using two ELISA systems which were protein or carbohydrate based. Corresponding serum samples were examined for systemic immune responses by using a microscopic agglutination test (MAT) and IgG-ELISA tests. Antigen was detected by direct immunofluorescence in six of the 163 samples of cervico-vaginal mucus. Both IgG and IgA antibodies were detected by ELISA in the genital discharges with a prevalence much higher than that obtained by the MAT but lower than that observed with the serum IgG-ELISA. Combining both groups, none of the MAT-positive cattle was negative by serum-ELISA. By using the protein or carbohydrate fraction serum IgG-ELISA assays, respectively, 29 or 41 per cent of the MAT-negative cows were positive at a titre of at least 1:40. Similarly, eight or 23 samples (10 or 27 per cent) had titres of at least 1:20 in the genital discharge ELISA for IgG and IgA antibodies, respectively. The serum IgG-ELISA was the most efficient in detecting hardjo antibodies, but in group 2 the IgG- and IgA-ELISA of the post calving discharge proved to be equally effective.

The efficacy of dihydrostreptomycin in stopping the shedding of Leptospira hardjo subtype hardjobovis was studied in naturally infected cows. Blood and urine samples were collected from dairy cows kept on a farm where the farmer had contracted L hardjobovis infection. A microscopic agglutination test and an ELISA were used to determine specific antibody responses in serum. Polymerase chain reaction was used to detect bacterial shedding in urine. On the first sample collection date, 6 cows were seropositive, and 3 of those shed leptospires in the urine. These 3 cows were treated once with 25 mg of dihydrostreptomycin/kg of body weight. Within 1 week, the 3 cows stopped shedding leptospires. Six weeks later, 8 more lactating cows were found to be shedding leptospires. These cows were also treated once with dihydrostreptomycin, and they too stopped shedding leptospires within 1 week. From then on, the whole herd was examined weekly for a period of 2 months, and all cows Leptospira-positive by polymerase chain reaction were treated once with dihydrostreptomycin. Again, all cows stopped shedding leptospires in the urine within 1 week after treatment with dihydrostreptomycin. After a single treatment of the whole herd at the same time, new infections were not seen.

Correlations between neutrophilic enzymes (acid and alkaline phosphatases, myeloperoxidase, NBT test) and lymphocyte and monocyte enzymes (acid phosphatase, nonspecific esterase) were studied in 110 patients with icterohemorrhagic leptospirosis. These correlations were changing, depending on the disease severity and period. In case of a favorable course of leptospirosis in the initial period and at the peak a great number of intercellular correlations are formed between neutrophilic, lymphocytic, and monocytic enzymes. If the disease course is grave and complicated the intercellular relationships are ruptured at the peak of the illness. Convalescence is characterized by a gradual recovery of intracellular correlations.

Erythrocyte osmotic fragility (EOF) was carried out in nineteen dogs naturally infected by Leptospira interrogans serovar icterohaemorrhagiae/copenhagi. A decreased EOF was observed, suggesting a modification of erythrocyte components secondary to disturbances that occur during canine leptospirosis, such as renal damage and hepatic disease.

Two patients are described with Weil's disease as a rare cause of jaundice. We discuss some features that can lead to early diagnosis. This concerns the apparently aspecific flu-like syndrome that precedes the icteric phase of the disease, as well as the typical pattern of liver function tests in the jaundiced patient: serum bilirubin is markedly elevated as compared with the liver enzymes. Another clue to the diagnosis can be obtained by enquiring not only about the patient's profession, but also about his leisure activities, since both patients acquired the disease in their leisure time.

Leptospiral antibody prevalence was 16% in residents of Baltimore. Seropositivity was associated with age, gender, race, and bird ownership, reduced the antibody risk associated with age and race from odds ratios (95% confidence interval) of 3.3 (2.0, 5.5) and 3.3 (1.1, 9.3), respectively, to the baseline level. These data establish the high prevalence of leptospiral antibody in Baltimore and suggest a protective role for cats in reducing the risk of human infection.

Guinea pigs were intravenously injected with icterhemorrhagiae serogroup Lai serovar strain 017 leptospirosis to model the pulmonary diffuse hemorrhage (PDH) in leptospirosis. Thirty-eight hours after the injection, the jugular arteries were catheterized to collect blood sample. The plasma was prepared for radioimmunoassay of TXB2 and 6-keto-PGF1a, the stable metabolites of TXA2 and PGI2 respectively. The plasma level of TXB2 in the experimental group, 107.15 +/- 41.65 pg/ml (n = 7), almost doubled that of the control, 54.05 +/- 12.93 pg/ml (n = 7), with significant difference (P less than 0.01); meanwhile, no significant difference was observed of 6-keto-PGF1a, 67.97 +/- 16.89 pg/ml (n = 6) vs. 98.06 +/- 40.63 pg/ml (n = 9) with P greater than 0.1. The fact that TXA2 causes vasoconstriction and increases vessel permeability suggests that TXA2 elevation should play a role in the mechanism of PDH in leptospirosis.

The authors describe a rare case from the clinical practice. Treatment including hemosorption was employed in a 38-year-old with a severe form of icterohemorrhagic leptospirosis accompanied by acute reno-hepatic failure and pronounced thrombocytopenia--15 x 10(9)l. The relative significance of thrombocytopenia as one of the main contraindication to hemosorption is suggested.

Leptospirosis is a zoonosis with protean clinical manifestation. Diagnosis requires a high index of suspicion and is confirmed by isolation of the organism or, more commonly, by serologic studies. In the fall of 1987, after severe flooding, we saw 93 patients with leptospirosis, confirmed by a microagglutination test. Thirteen percent of the patients had no clinical or laboratory findings except fever and headache, but the rest had mild to severe manifestations. Jaundice, renal failure, and aseptic meningitis were not common, but pulmonary symptoms, when present, were striking. The mortality rate was 5%. The main cause of death was asphyxiation due to massive hemoptysis from pulmonary hemorrhage and acute respiratory failure.

Leptospira interrogans serovars balcanica and tarassovi both induced mild subclinical infections in grivet monkeys. The activities in serum of lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase and the level of alpha 1-antichymotrypsin increased in a few days after infection. Concomitant decreases in serum iron levels were observed in some cases. These changes occurred in the absence of any observable clinical signs though there were histopathological lesions in some organs. No haematological changes or alterations in other sreum components were detected.

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.

Irradiated hamsters were infected with Leptospira interrogans serovar ballum in order to study the effects of impairment of the reticulo-macrophage system on the progression of the disease and the development of haemoglobinaemia. Infected and irradiated hamsters were compared with infected controls, irradiated controls and untreated controls. Red blood cells (RBCs) from untreated controls were biconcave disks while those from irradiated controls were echinocytes. Red blood cells from animals of both infected groups which were severely affected and moribund were in the form of pitted spherocytes and were associated with increased icteric indices and haemoglobinaemia. Red blood cells from less severely affected animals were echinocytic. Pitted spherocytes, however, were seen in some irradiated-infected hamsters before increased icteric indices and haemoglobinaemia were present. Both irradiated-infected and irradiated hamsters showed severe depletion of haemopoietic cells and lymphoid cells, with regeneration occurring in those animals which survived for longer. Red cell sequestration and erythrophagocytosis were present in infected-only hamsters. In irradiated-infected animals, severe anaemia was caused by both persistence of fixed macrophages, RBC sequestration and erythrophagocytosis, and haemorrhage due to vascular damage and renal papillary necrosis. A severe leucopaenia affected the irradiated hamsters' ability to suppress leptospiral multiplication resulting in the presence of larger numbers of organisms.

Fourteen cases of leptospirosis due to the Leptospira interrogans serogroup Icterohaemorrhagiae (Weil's disease) were serologically confirmed in the last 15 years. In two cases, Icterohaemorrhagiae was also isolated from the patients' blood. Both positive cultures were obtained in Korthof's medium by indirect passage through brain-heart infusion medium. One of the isolates was identified as serovar budapest, which has never been reported in Israel. In most of the cases, paradoxical cross-reactions with serovars of the Autumnalis, Hebdomadis and Canicola serogroups were observed in the early stages of the illness. In all cases, we suspected that the source of the infection was serovars of the Icterohaemorrhagiae serogroup shed in the urine of Rattus norvegicus rats. Thirteen of the affected persons were working and living in the Tel Aviv area, all in places not known to be Icterohaemorrhagiae endemic before 1968. One patient was working and living in the Hadera region. All patients were jaundiced, and one died. The illness was usually accompanied by pronounced and long-lasting elevation of blood bilirubin and urea levels.

The intramuscular vaccination of pigs with two doses, two weeks apart, of a Leptospira interrogans serovar bratislava bacterin, protected pigs against renal infection when challenged with bratislava strains six weeks later but did not protect pigs challenged after 26 weeks.

Haemoglobinaemia is seen in certain hosts infected by certain serovars of Leptospira interrogans, but is absent from other serovar-host associations. Comparisons were made between calves infected with serovar pomona and those receiving a crude "toxin" prepared from the same organism. Red blood cells from "toxin"-injected calves showed discocyte-echinocyte transformation and contained portions of cytoplasm segregated within vacuoles. These animals showed increased sequestration of RBCs within the spleen but no overt haemoglobinaemia. Red blood cells from infected and haemoglobinaemic animals were spherical and pitted. They also showed vacuoles and tracts under the cell membrane in fully haemoglobinized RBCs and dark granular inclusions within the cytoplasm of those which were only partially haemoglobinized. Intracellular leptospires were not seen within the RBCs. Red blood cell sequestration and erythrophagocytosis were very pronounced within the spleen, liver and bone marrow. The changes in the RBCs are not easily explained by the previously proposed theory that RBC destruction is due to a phospholipase-like toxin acting directly upon the RBC membrane. A more appropriate hypothesis is that the RBC lesions are due to the adverse effects of leptospiral "toxin(s)" on the metabolism of the RBC causing the formation of defective portions of cytoplasm. These are then either degraded and expelled, leaving empty vacuoles, or are degraded and left within the cytoplasm as dark granular inclusions.

14 cases of leptospirosis ictero-haemorrhagica observed on Reunion island with predominant or isolated pulmonary symptoms are described. Hospitalisation was motivated in every case by haemoptysis, at times profuse, which occurred in patients with fever and myalgia. The chest radiographs revealed an alveolar and/or a bilateral alveolar pattern of variable severity. In spite of the importance of chest radiography port raying an extensive and serious pneumonia in one case out of every two, the outcome was favourable with a mean time lag of one week. In three cases, an adult respiratory distress syndrome (ARDS) was seen requiring assisted ventilation and one death occurred. The diagnosis of leptospirosis may be considered, even in countries of low endemicity, in a case pneumonia with extensive haemoptysis or an adult respiratory distress syndrome whose cause is not established by the usual tests.

Inoculation of 2 groups of dogs with 1 X 10(9) and 4 X 10(9) Leptospira interrogans serovar icterohaemorrhagiae produced disease varying from transient fever to uremia and death. Clinical signs of disease in the severely affected dogs were fever, dehydration, depression, and icterus. Laboratory changes in serum of infected dogs included increased urea nitrogen, creatinine, phosphorus, alkaline phosphatase, total bilirubin, aspartate aminotransferase, and alanine aminotransferase. Chloride concentration decreased in the serum of dogs with severe disease. The icterus in the infected dogs did not appear to be related to hemolytic anemia.

Serum bile acids have been measured in patients with a wide variety of liver diseases using a technique which separates the major individual conjugated and free bile acids. Total serum bile acids may be elevated up to 100 times the normal concentration in patients with liver disease and this increase consists largely of conjugated bile acids. The ratio of glycine-conjugated to taurine-conjugated bile salts is low in all types of liver disease and this is found particularly in the serum of patients with obstructive jaundice. There is a decrease in the ratio of trihydroxy:dihydroxy cholanic acid in patients with cirrhosis.