Pressor support during a Jarisch Herxheimer reaction after initiation of treatment for Weil's disease.

We present a case of Weil's disease complicated by a Jarisch-Herxheimer reaction (JHR) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. The case is followed by a brief review of the JHR which is rarely observed with treatment of leptospirosis. A healthy 28-year-old female who recently returned from the Caribbean presented to the emergency department with flu-like symptoms. The patient appeared jaundiced with conjunctival suffusion and was ultimately treated with the appropriate antibiotics for leptospirosis in the ED. She decompensated subsequently, requiring supplemental oxygen, central and arterial line placement, and vasopressor support with norepinephrine. Although rarely encountered and not well reported throughout the literature, initiation of antibiotics can cause a JHR reaction given that Leptospira interrogans is a spirochete. This JHR may be self-limited and of short duration, or it can be prolonged and severe, requiring invasive therapies such as central line placement for vasopressor support and intubation. It is suggested that patients started on antibiotics for leptospirosis/Weil's disease should be monitored in the emergency department for a short duration prior to discharge or transfer to a regular medical floor for observation given the possibility for decompensation.

Weil's disease presenting as atypical pneumonia.

Leptospirosis is a disease caused by spp. Leptospira, also known as Weil's disease if it manifests with jaundice. It can be associated with respiratory, renal, hepatic and haematological complications and most importantly carries a high mortality when untreated. We describe a case of a 53 year old man presenting with myalgia and fever in whom the diagnosis of leptospirosis was not initially considered. Following a deterioration in his condition a careful history revealed an apparent brief exposure to animal urine and subsequent grossly positive Leptospira serology. Treatment of his condition led to complete resolution after a brief stay on the intensive care unit. This case highlights the atypical nature of a presentation of Leptospirosis, its respiratory complications, and importance of serological testing in its diagnosis.

Human hemorrhagic pulmonary leptospirosis: pathological findings and pathophysiological correlations.

BACKGROUND: Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil's syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. PRINCIPAL FINDINGS: Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. CONCLUSIONS: Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease.

Leptospirosis presenting as acute meningoencephalitis.

Leptospirosis in humans is a common zoonotic disease. It is often under-diagnosed, especially when associated with neurological features, resulting in significant morbidity and mortality. This subgroup of patients with neurological manifestations is often empirically treated for cerebral malaria, dengue fever, tuberculous meningitis, hepatic encephalopathy, viral encephalitis, etc. Hence it is important to be aware of uncommon manifestations of this disease. We report one such patient, which highlights the importance of considering leptospirosis as the diagnostic possibility with hepato-renal, pulmonary and nervous system involvement, particularly where diagnostic supports and resources are limited.

Leptospiral nephropathy.

Leptospirosis is recognized as a globally re-emerging zoonosis. Interstitial nephritis is the principal feature of the disease. Leptospirosis-induced acute kidney injury typically is nonoliguric and includes hypokalemia. Tubular function alterations precede a decrease in the glomerular filtration rate, which could explain the high frequency of hypokalemia. Studies in human beings and animals have shown increased urinary fractional excretion of potassium and sodium, as well as an increased potassium/sodium ratio, suggesting increased distal potassium secretion caused by increased distal sodium delivery consequent to functional impairment of proximal sodium reabsorption. Confirming these findings, Western blot studies have shown lower renal expression of the sodium/hydrogen exchanger isoform 3 and of aquaporin 2, together with higher renal expression of the Na-K-2Cl cotransporter NKCC2, in infected animals. The severe form (Weil's disease) manifests as diffuse alveolar hemorrhage, pulmonary edema, acute respiratory distress syndrome, or a combination of these features, accompanied by acute kidney injury and can be highly lethal. Antibiotic treatment is efficient in the early and late/severe phases. For critically ill leptospirosis patients, the following are recommended: daily hemodialysis, low daily net fluid intake (because of the risk for pulmonary hemorrhage), and lung-protective strategies (low tidal volumes and high positive end-expiratory pressures after recruitment maneuvers).

Reversal of renal tubule transporter downregulation during severe leptospirosis with antimicrobial therapy.

Tubular dysfunction is a hallmark of severe leptospirosis. Antimicrobial therapy is thought to interfere on renal involvement. We evaluated the expression of a proximal tubule type-3 Na+/H+ exchanger (NHE3) and a thick ascending limb Na+-K+-2Cl(-) cotransporter (NKCC2) in controls and treated hamsters. Animals infected by a serovar Copenhageni isolate, were treated or not with ampicillin (AMP) and/or N-acetylcysteine (NAC). Leptospiral antigen(s) and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen(s) in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. NAC effect was restricted to lowering TBARS. Early and late AMP treatment rescued tubular defects in severe leptospirosis disease, and there was no evidence of benefit from antioxidant therapy.

Hallazgo de infecciones concomitantes leptospira-fiebre amarilla y leptospira-dengue en casos de pacientes fallecidos con síndrome febril icterohemorrágico en Venezuela años 2003-2004 / Discovery of concurrent infections leptospira-yellow-fever and leptospira-dengue in cases of deceased patients with febrile icterus syndrome in Venezuela during 2003-2004

Como parte del programa de vigilancia epidemiológica del Ministerio de Salud y Desarrollo Social, el Instituto Nacional de Higiene "Rafael Rangel" realiza el diagnóstico diferencial de los síndromes febriles hemorrágicos e ictero-hemorrágicos, los cuales incluyen la determinación de leptospirosis, dengue, fiebre amarilla, hepatitis entre otros. En Venezuela se han presentado numerosos casos de dengue que mantienen los índices a nivel epidémico, contínuos brotes de leptospirosis y algunos brotes de fiebre amarilla en los dos últimos años. La participación en este programa de vigilancia permitió detectar 5 casos de fallecidos durante los años 2003 y 2004 con resultados de laboratorio que indicaban posibles infecciones concomitantes de leptospirosis con dengue o leptospirosis (N) con fiebre amarilla, lo que podría explicar la severidad de los cuadros clínicos y la muerte de los pacientes. De un total de cinco (5) casos que resultaron positivos a leptospirosis por la técnica PCR, cuatro (4) de ellos resultaron con IgM positiva a fiebre amarilla, y uno (1) con IgM y PCR positivo a dengue. Los cuatro (4) casos, IgM positivos a fiebre amarilla, tenían resultados histopatológicos compatibles a infección viral tipo fiebre amarilla y el caso N° 4 se logró confirmar el diagnóstico de fiebre amarilla por inmunohistoquímica. Este hallazgo indicaría que estamos en presencia de cuatro casos de coinfección leptospira-fiebre amarilla. Por otra parte, el último caso resultó positivo con la prueba de ELISA IgM para dengue con PCR positivos tanto a leptospira como a dengue y con una prueba género específica empleada en el diagnóstico precoz de la leptospirosis (antígeno TR) igualmente positiva, lo que indicaría igualmente un caso de coinfección leptospira-dengue. En la literatura científica existen reportes de posibles coinfecciones leptospira-dengue que no han sido bien documentadas, sin embargo, infecciones concomitantes entre leptospira y fiebre amarilla no han sido reportadas.

Serological study of the frequency of leptospiral infections among dairy cows in farms with suboptimal reproductive efficiency in Galicia, Spain.

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.

Enfermedad de Weil

Presentamos el caso de una mujer de 29 años, de un sector subnormal de Neiva con un cuadro de fiebre, dolores musculares, ictericia, hemorragia de vías digestivas, sin compromiso hemodinámico y falla renal aguda. La M.A.T. fue positiva para 4 serovars con títulos mayores de 1/800 diluciones. Este es uno de los pocos casos informados en la literatura, causada por múltiples serovars.

Risk factors for death and changing patterns in leptospirosis acute renal failure.

The risk factors for death and changes in clinical patterns in leptospirosis (Weil's disease) have not been well studied. We retrospectively studied 110 patients with Weil's disease hospitalized in Brazil between 1985 and 1996. Univariate statistical analysis showed that nonsurvivors were older than survivors, and had higher frequency of oliguria, cardiac arrhythmia, dyspnea, and pulmonary rales. Logistic regression showed that the only independent factor associated with death was oliguria (odds ratio [OR] = 8.98). The presence of arthralgia (OR = 4.71), dehydration (OR = 6.26), dyspnea (OR = 17.7), and pulmonary rales (OR = 9.91) increased after 1994. These data suggest that in Weil's disease the clinical patterns have changed and the presence of oliguria is a risk factor for death.

[The role of rheohepatography in assessing liver function in leptospirosis]. / Rol' reogepatografii v otsenke sostoianiia pecheni pri leptospiroze.

A rheographic investigation on the liver in patients with leptospirosis revealed substantial disturbances in the system of hepatic circulation, which observation was regarded as corresponding to gross morphologic changes in the liver. Potentialities are shown of hepatorheography in assessment of severity of injury to the liver and degree of its return to normal in leptospirosis.

[The clinical aspects of discrete plasmapheresis in treating multiple organ failure in patients with the icterohemorrhagic form of leptospirosis]. / Klinicheskie aspekty diskretnogo plazmafereza v lechenii poliorgannoi nedostaochnosti u bol'nykh s ikterogemorragicheskoi formoi leptospiroza.

Discrete-mode plasmapheresis using medium doses of separated plasma provides a detoxicating effect by eliminating of toxins, products of catabolism, biologically active substance, stimulation of gastrointestinal functions and cardiovascular system. Clinical application of plasmapheresis in a combined treatment of leptospirosis icterohaemorrhagica under multiorgan failure offers a highly efficient therapeutic alternative in alleviating the condition.

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).

Weil's disease: report of 12 cases.

The epidemiological distribution and clinical features of 12 cases of Weil's disease from Turkey, are reviewed. The disease is most common in male farmers from rural areas. Myalgia and jaundice were recorded in all patients. Signs included vomiting in 9 patients, haemorrhages in 6, and renal function was impaired in 6. Creatine phosphokinase levels were found above normal limits in 75% of the cases. Leptospires were demonstrated with dark-field microscopy in the blood of 9 and in the urine of 5 of these patients. The diagnosis was confirmed with microscopic agglutination test (MAT) as well as with ELISA. Ig M antibodies were detected in 11 (92%) of the patients and is an accurate marker for acute leptospirosis. Penicillin was used for therapy and the outcome was favorable in 10 patients. Two patients died. It should be kept in mind that leptospirosis is an extremely severe disease which requires appropriate examinations at the right moment.

Weil's disease as a cause of jaundice.

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.

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.

[Electrocardiographic changes in leptospirosis]. / Elektrokardiograficheskie izmeneniia pri leptospiroze.

The study involved 239 ECGs recorded in acute period of various leptospirosis forms. In 86.2% of cases there were changes evidencing impairment of neuromuscular system and atrial (76.6%) or ventricular (61.9%) conduction. The above cardiac manifestations arise early, have peculiar characteristic features. The discussion covers their patho- and morphogenesis, frequency of detection, necessary time-course ECG control over leptospirosis patients and convalescents.