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Evaluation of diagnostic tests for human leptospirosis.

The IgM-PK-ELISA, an enzyme-linked immunosorbent assay for immunoglobulin M employing a proteinase K-treated antigen, and the "Leptoteste-S" macroagglutination test were evaluated for use in a rapid serodiagnosis of human leptospirosis. The microscopic agglutination test (MAT) was used as reference. The three serological tests were applied to serum samples from patients with leptospirosis (N = 89), typhoid fever (N = 8), malaria (N = 19), syphilis (N = 20), hepatitis (N = 16) and from clinically healthy donors (N = 92). The overall results of the IgM-PK-ELISA and the "Leptoteste-S" are comparable to those of the MAT. However, both tests differed statistically from MAT in terms of the positivity of the acute-phase sera, with approximately 38% of the patients with leptospirosis being identified earlier than when MAT was used. The IgM-PK-ELISA, with 89.9% sensitivity and 97.4% specificity, could be the test of choice for those laboratories which are equipped to perform ELISA. The "Leptoteste-S", with 89.9% sensitivity and 94.8% specificity, seems to be easier to perform and the most accessible to peripheral laboratories for rapid screening of human sera. Both techniques present the important characteristic of detecting early antibodies against leptospires, thus providing a diagnosis during the early stages of the disease.

Agglutination Tests↗

Preliminary survey of Leptospirosis and Lyme disease amongst febrile patients attending community hospital ambulatory care in Maputo, Mozambique.

OBJECTIVES: To evaluate the importance of the spirochetes Leptospira interrogans s.l. and Borrelia burgdorferi s.l., as causes of human diseases (leptospirosis and Lyme borreliosis), in order to guide the development of laboratory services and patient management and to identify the appropriateness of future epidemiological studies. DESIGN: Cross sectional serological survey. SETTING: Maputo, the capital city of Mozambique. SUBJECTS: 160 adult patients (18 to 50 years of age) presenting, sequentially and for the first time, with a febrile illness at the outpatient's department of a community hospital. METHODS: All sera were examined for L. interrogans s.l. antibodies by the standard microtiter technique (MAT), using as live culture antigens a battery of serovars representing 20 pathogenic serogroups. The IgM and IgG antibody response to B. burgdorferi s.l. was determined in all sera with an indirect IgG ELISA. In order to study potential serological cross-reactivity in malaria positive sera, all samples were further examined for antibodies against Plasmodium falciparum by indirect immunofluorescence. This was complemented with a standardised clinical history and physical examination. MAIN OUTCOME MEASURES: Presence of antibodies to Leptospira interrogans s.l. and to Borrelia burgdorferi s.l.. RESULTS AND CONCLUSIONS: Although not conclusive, because of the inability to attempt rising serology and positive cultures, the results suggest that 10% of non-specific febrile illnesses could be attributed to leptospirosis. This study may thus form the background for a definitive Leptospira research in the same location. We confirm reports from other African countries that Lyme disease is an unlikely occurrence. We further suggest that some of the seropositivity observed for Lyme disease in Maputo could be attributed to serological cross reactivity with antibodies to P. falciparum malaria, leptospirosis or syphilis.

Adolescent↗

[Leptospirosis epidemic (L. grippothyphosa) in the Mainz area, concerning the pediatric age group (author's transl)].

31 children, presenting with rather uncharacteristic symptoms of an infectious disease and being referred to this clinic mostly because of lymphadenitis of the neck (81%) and/or signs of meningitis (45%), were seen within a period of only eight weeks and proved to suffer from Leptospirosis (L. grippotyphosa). The majority of the patients belonged to the age group of one to six years and lived in rural environs. Our observation is considered to relate to a Leptospirosis epidemic and suggests, as opposed to the general acceptance, a much higher incidence of Leptospirosis in this country and, moreover, in children.

Ampicillin↗

Vascular damage in acute experimental leptospirosis of the guinea-pig.

The pathogenesis of the haemorrhagic diathesis in experimental leptospirosis of the guinea-pig was investigated in the lung, diaphragm and kidney. The vascular damage was found to be focal and mainly capillary. Swollen endothelium with dilated endoplasmic reticulum, enlarged mitochondriae and open junctions seemed to be the initial lesions and endothelial necrosis the final picture in all tissues. The lung capillaries showed endothelial and epithelial blebs and desquamation with many myelin figures. Capillary thrombosis was observed in the pulmonary microcirculation, probably acting as an aggravating factor and being partly responsible for the particularly impressive lung haemorrhages. The peritubular renal capillaries as well as open junctions and gaps due to necrosis also had enlarged fenestrae which were permeable to colloidal carbon particles. The paucity of micro-organisms in the vicinity of the lesions is in accordance with the toxic genesis postulated for the vascular damage in leptospirosis. It is suggested that the vascular lesions induced by leptospirosis begin with increased permeability prior to endothelial necrosis.

Acute Disease↗

Clinical observation and treatment of leptospirosis.

The epidemiological and clinical observations of 240 patients with Weil's disease and 10 patients with canicola fever, and these observations in two epidemics of canicola fever, are presented. Early diagnosis is most important for the prognosis of patients with the severe form of leptospirosis. It depends on the clinical features, clinical laboratory findings, and the epidemiological situation. The most characteristic clinical signs for early diagnosis were febrile illness of sudden onset, severe general malaise, muscular pain, and conjunctival congestion. Proteinuria, leukocytosis with neutrophilia, and raised erythrocyte sedimentation rate were the most indicative clinical laboratory findings for early diagnosis. Although jaundice and hemorrhage are the most important signs of the severe form of leptospirosis, Weil's disease, these are rarely useful in early diagnosis. Of a variety of antibiotics used, penicillins and cephems had the lowest minimal inhibitory concentration against leptospires. However, it became apparent from basic studies in vitro and in vivo that streptomycin showed the best bactericidal action against leptospires and that it was the most effective anti-leptospiral antibiotic. Gentamicin, tobramycin, and isepamicin are also effective as alternatives to streptomycin. Although penicillins, cephems, tetracyclines, and macrolides are also effective for the treatment of leptospirosis, when these antibiotics with inadequate bactericidal activity are used for the treatment of the disease, long-term therapy with sufficiently large doses may be required from an early stage of the disease until the appearance of antibodies.

Animals↗

Leptospirosis in the tropics and in travelers.

Leptospirosis, caused by spirochetes of the genus Leptospira, has increasingly been recognized to affect travelers and residents in tropical settings. A zoonotic disease, leptospirosis is transmitted to humans through environmental surface waters contaminated by the urine of chronically infected mammals. Outcome of infection varies, ranging from acute febrile illness (including self-resolving undifferentiated fever) to aseptic meningitis to a fulminant syndrome of jaundice, oliguric renal failure, pulmonary hemorrhage, and refractory shock. Hospitalized cases have mortality rates as high as 25%. A recent clinical trial showed that third-generation cephalosporin is as effective as doxycycline and penicillin in the treatment of acute disease. Doxycycline is effective in preventing leptospirosis in travelers. No protective vaccine is currently available.

Journal Article↗

Leptospirosis: II. Investigation of clinical disease in dairy cattle in the Waikato district of New Zealand.

Investigations were carried out in 1975, 1976 and 1977 in 16 dairy herds where leptospiral abortions were suspected and in five other herds where clinical disease was not present. Both Leptospira interrogans serovars pomona and hardjo were isolated from cattle in herds with leptospirosis, but only pomona was recovered from those that had aborted. There was no evidence that hardjo caused clinical disease in dairy cattle in the Waikato district. It was found that 73% of the cows that aborted and 19% of other animals in the same herds had microscopic agglutination test titres to pomona of 1:2,000 or greater. By contrast, only 2% of cattle in herds without clinical evidence of leptospirosis had such titres. One cow retained a titre of 1:2,000 or greater to pomona for 7 months; titres of this order had a shorter duration in other cows. Leptospiruria occurred in 50% of cows that had aborted and in 9% of in-contact cows in the same herds. Only 0.7% of cows had leptospiruria in the herds with no clinical disease. Ten of 35 cows shedding pomona still had leptospiruria one month later. It was concluded that clinical leptospirosis should be diagnosed by testing a sample of the herd, rather than just individual cows, because of the variability and persistence of leptospiruria and serological titres in cows with and without clinical signs. Although hardjo is common in cattle in the Waikato district, it was not found to cause abortion in cattle.

Journal Article↗

Leptospirosis vaccination in beef cattle: use of decision tree analysis.

Decision tree analysis was used to evaluate the economic benefits of leptospirosis vaccination in beef cattle. The analysis used estimated values for the cost of vaccination, the probability of calf losses from leptospirosis and the economic losses resulting from calf mortality to calculate the expected value of vaccination. A computer spreadsheet was used to calculate the expected value of the vaccination programme over a wide range of estimated costs and probabilities and to determine the break-even point at which vaccination becomes economic. A sensitivity analysis demonstrated that the outcome of the analysis was most dependent on calf value and the probability of calf loss due to leptospirosis. The analysis was relatively insensitive to changes in vaccine cost, vaccine efficacy and herd fertility.

Journal Article↗

Potential benefit of plasma exchange in treatment of severe icteric leptospirosis complicated by acute renal failure.

Leptospirosis is a common zoonosis seen worldwide, but it is rare in our locality (Hong Kong). Clinical manifestations of leptospirosis are variable and may range from subclinical infection to fever, jaundice, hemorrhagic tendency, and fulminant hepato-renal failure. Severe hyperbilirubinemia and acute renal failure have been associated with high mortality. We report our experience with a patient who developed severe Weil's syndrome with marked conjugated hyperbilirubinemia and oliguric acute renal failure. These complications persisted despite treatment with penicillin and hemodiafiltration. Plasma exchange was instituted in view of the severe hyperbilirubinemia (970 micromol/liter). This was followed by prompt clinical improvement, with recovery of liver and renal function. The beneficial effects of plasma exchange could be attributed to amelioration of the toxic effects of hyperbilirubinemia on hepatocyte and renal tubular cell function. We conclude that plasma exchange should be considered as an adjunctive therapy for patients with severe icteric leptospirosis complicated by acute renal failure who have not shown rapid clinical response to conventional treatment.

Acute Kidney Injury↗

Is CK-MB isoenzyme useful for diagnosis of cardiac involvement in icteric leptospirosis?

In the absence of heart failure or cardiogenic shock, cardiac involvement diagnosis in icteric leptospirosis is possible on the basis of abnormal electrocardiograms. As metabolic and electrolytic disorders are frequently seen during acute leptospirosis infection, they may be responsible for some electrocardiograms changes. We conducted a study to assess if creatine phosphokinase isoenzyme determinations are useful in selecting patients with a high cardiac involvement suspicion. Sixty-nine patients were studied prospectively. Ten patients out of 16 with cardiac involvement and 25 without had high CK-MB levels (p > 0.05), although mean values of abnormal CK-MB levels were higher in the group with cardiac involvement (p < 0.05). Our analysis indicates that serum CK-MB determination does not provide a specific indicator of myocardial involvement in the course of icteric leptospirosis.

Adult↗

Leptospirosis mimicking sepsis after orthopedic surgery: a case report.

We report a case of leptospirosis that occurred after elective surgery involving tendon transfer and shoulder arthroscopy. The disease mimicked hospital infection after orthopedic surgery and was at first misdiagnosed as post-operative sepsis. The patient was 60 year old female that developed sepsis with hypotension, shock, bleeding, jaundice and renal insufficiency 4 hours after surgery. Shock treatment procedures were performed and broad spectrum antibiotic therapy was used with coverage for bacteria acquired in hospitals. A careful investigation was carried out by the Hospital Infection Control Service in search of the possible source of the infection. After clinical evaluation by a specialist in infectious diseases, the hypothesis of leptospirosis was put forward based on clinical and epidemiological data. The hypothesis was later confirmed by the positive result of serological tests with the microagglutination method that yielded 1:800 and then 1:12,600 7 days later. This is the first reported case of leptospirosis manifest directly following surgery, mimicking postoperative sepsis.

Arthroscopy↗

Leptospirosis in the Seychelles.

OBJECTIVE: To ascertain the incidence of leptospirosis in the Seychelles, identify its sources, review diagnostic features and assess complications. DESIGN: A prospective survey over a two-year period 1988-1990 of all cases diagnosed as having leptospirosis at Victoria Hospital, the main referral hospital for the Islands. RESULTS: Eighty cases were diagnosed on clinical grounds with serological confirmation in 58 (73%). Leptospira interrogans serovar icterohaemorrhagiae was identified in 27 (33%) and serovar autumnalis in 2 (3%), there was broad cross-reactivity in the other specimens. In a further 7 (9%), the diagnosis was confirmed at autopsy. Useful diagnostic aids were the finding of myalgia in 68 (85%) and a raised creatine phosphokinase (CPK) level in 61 (76%). CPK elevation was found to be a more reliable indicator of disease the earlier in the illness it was measured. Other important clinical signs are reviewed. Sixty (76%) were regular drinkers suggesting a relationship with home-brewed alcohol, 48 (60%) were in at-risk occupations; 13 (16%) deaths resulted. CONCLUSIONS: Leptospirosis in the Seychelles is likely to be rat borne. An annual incidence of 60 per 100,000 was found with significant mortality. Muscle tenderness and raised CPK levels were the most reliable early diagnostic aids.

Adult↗

[Leptospirosis: a frequently missed diagnosis? Epidemiology and diagnosis in Switzerland].

Clinical leptospirosis is rarely seen in Switzerland due to the climatic conditions. Nevertheless people may still suffer from leptospirosis, even to the extent of requiring intensive medical treatment. Variable symptoms and problematic diagnostics can make the diagnosis of leptospirosis difficult. Through two cases with varied symptoms, the clinical and diagnostic features of the disease are presented. In addition, the risk factors, the epidemiology and the diagnostic possibilities are discussed.

Adult↗

[Cardiogenic shock due to acute myocarditis complicating leptospirosis].

A 48 year old man was admitted to the intensive care unit with septicaemic shock associated with febrile jaundice and anuric renal failure. Within hours, he developed cardiogenic shock with multi-organ failure due to an acute myocarditis refractory to catecholamines and requiring intra-aortic balloon pumping. The diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was finally favourable. Myocarditis is an underestimated complication of leptospirosis because it is often symptomless. The main signs are arrhythmias, conduction defects and ST-T wave abnormalities which have little clinical expression. The disease may progress and is sometimes fatal. Leptospirosis myocarditis should therefore be carefully considered because of its potential severity and its reversibility with appropriate antibiotic therapy and also the necessity of initial management in a specific infrastructure.

Humans↗

[Plasma PGI2 and TXA2 levels on a model of PDH in leptospirosis].

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.

6-Ketoprostaglandin F1 alpha↗

[Leptospirosis caused by Leptospira icterohaemorrhagiae of the pseudo-surgical type: a case].

The authors report a case of fatal leptospirosis due to Leptospira icterohaemorrhagiae revealed by typical signs of acute cholecystitis and associated with pancreatitis in a 73 year old patient presenting with gallstones. The initial clinical findings were highly suggestive of severe but typical cholecystitis and the final diagnosis was only considered when the patient's condition worsened despite surgery, with increasing obstructive jaundice and multiple organ failure. Pancreatitis was an autopsy finding. Misleading, especially gastrointestinal symptoms are frequent in leptospirosis. Hence an early diagnosis is an essential condition for a successful antibiotic management in severe cases of leptospirosis. This possibility should be considered whenever a patient presents with infectious obstructive jaundice. The patient has to be questioned concerning possible contact with contaminated animals and, when in doubt, the presence of specific antibodies should be investigated.

Acute Disease↗

[Respiratory complications of leptospirosis. Apropos of 6 cases, 3 of which show hemodynamic studies].

Six cases of leptospirosis with pulmonary complications are reported. Three cases were accompanying an hepato-nephritis due to L. icterohaemorrhagiae. The first patient died with massive hemoptysis. The second, presenting a bilateral pneumopathy predominant on the left side, recovered after plasma exchange and hemofiltration. The third case concerned a pulmonary edema complicating a vascular refilling in a shock syndrome it simply recovered. The three other cases were observed in an anicteric leptospirosis: in two cases, L. Australis was responsible; in the last, L. icterohaemorrhagiae was involved. The first patient had a radiologic picture simulating miliary tuberculosis. The second had pulmonary edema complicating a vascular refilling in a shock syndrome. The last was an acute respiratory distress syndrome, treated with artificial ventilation with penicillin therapy and corticotherapy. All these 3 patients recovered. The diagnostic, physiopathologic and therapeutic problems of these pulmonary complications of leptospirosis are discussed. The lesional nature of the pulmonary edema is proved by the low pulmonary wedge pressures observed with the Swan-Ganz Catheter.

Adult↗

Leptospirosis: a zoonotic disease of global importance.

In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.

Animals↗