Covid-19 and leptospirosis: Cytokine storm and the use of steroids.

The majority of patients with Covid-19 have a good outcome. However, complications principally of acute respiratory distress syndrome (ARDS) and multiple-organ failure can occur rapidly. Leptospirosis, a zoonotic disease, is similar to Covid-19 in that most infections are mild or asymptomatic and only a small number develop ARDS. Cytokine storm is considered to be the main incriminating factor in both. High dose steroids have been used to ameliorate the effects in leptospirosis, and similarly, reports suggest a benefit in Covid-19. SARS CoV-2 and leptospira, one a virus and the other a bacterium, are two species separated by millions of years of evolution, but producing illnesses with similar spectra, with cytokine storm being the common precipitating factor. As data are accrued from around the world, more light may be shed on features analogous to both pathways.

The Effect of Environmental Stresses on lipL32 Gene Expression in Pathogenic Leptospira spp. through Real-Time PCR.

Leptospirosis is a worldwide infectious and zoonotic disease. The incidence of this disease is high in temperate regions, especially in northern Iran. The aim of this study was to investigate the effects of temperature, pH, and Phyllanthus amarus plant extract on the lipL32 gene expression in pathogenic Leptospira spp. Fifty water samples were collected. Culture and PCR technique were used to isolate and identify the bacterium and the presence of the lipL32 gene. The samples were exposed to different temperatures and pH levels for one day and the Ph. amarus plant extract at different concentrations for one and seven days. RNA was extracted, and cDNA synthesis was performed for all the samples. All cDNAs were evaluated by the real-time PCR (SYBR green) technique. Out of the 50 samples, ten samples (20%), using PCR were determined to contain the pathogenic Leptospira. Fold change of the expression of the lipL32 gene associated with stresses was as follows: temperature stress of 40°C, 35°C, and 25°C reduced the lipL32 gene expression in all three isolates, especially in the isolates type 1. The pH stress, i.e., pH values equal to 8 or 9 reduced the gene expression in three types of isolates, and pH = 6 stress increases the lipL32 gene expression in the isolates of type 1. Ph. amarus plant extract stress reduced the mentioned gene expression only in isolates of type 2. Temperature and pH stresses could lead to differences in the expression level and cause the lipL32 gene expression decrease in three pathogenic isolates. The MIC results showed anti-leptospiral effect of Ph. amarus plant extract.

The preventable efficacy of ß-glucan against leptospirosis.

Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (ß-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of ß-glucan against Leptospira infection in hamsters. First, ß-glucan was administered 24 h prior to, during and after infection. The results showed that ß-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of ß-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1ß and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1ß and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, ß-glucan was administered 5 days prior to infection. ß-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that ß-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1ß and IL-6) in vitro, indicating that ß-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of ß-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.

Antimicrobial Resistance in Leptospira, Brucella, and Other Rarely Investigated Veterinary and Zoonotic Pathogens.

Leptospira, Brucella, and Borrelia are major agents of zoonotic disease, causing high morbidity and, in some cases, significant mortality in humans. For all three genera, prompt diagnosis and appropriate antimicrobial therapy are required to prevent the development of chronic, debilitating illness. Leptospira spp. are intrinsically resistant to several antimicrobial classes; however, there is little evidence in the literature for development of acquired resistance to antimicrobial agents used for clinical treatment of acute leptospirosis. For Brucella infections, there are numerous reports of relapses following therapy, but it is unclear whether this is due to sequestration within infected sites (e.g., bone) or the development of acquired resistance. Brucella have maintained their susceptibility to doxycycline and rifampicin, which in combination remain the most common treatments of brucellosis in humans. In vitro induced point mutations are described as imparting resistance to rifampicin (rpoB) and fluoroquinolones (gyrA). The clinical significance of these mutations is unclear. For Borrelia burgdorferi, although acquired resistance to some antimicrobial agents has been described, resistance due to bacterial persister cells surviving in the presence of antimicrobial, with no apparent increase in the MIC of the organism, have been recently described. Of the remaining veterinary fastidious pathogens, Lawsonia intracellularis is the most interesting from an antimicrobial resistance perspective because it can only be grown in cell culture, making in vitro susceptibility testing challenging. MIC testing has been undertaken on a small number of isolates, and some differences in susceptibility to macrolides have been demonstrated between isolates obtained from different regions.

Advances & challenges in leptospiral vaccine development.

Considerable progress has been made in the field of leptospiral vaccines development since its first use as a killed vaccine in guinea pigs. Despite the fact that the immunity conferred is restricted to serovars with closely related lipopolysaccharide antigen, certain vaccines have remained useful, especially in endemic regions, for the protection of high-risk individuals. Other conventional vaccines such as the live-attenuated vaccine and lipopolysaccharide (LPS) vaccine have not gained popularity due to the reactive response that follows their administration and the lack of understanding of the pathogenesis of leptospirosis. With the recent breakthrough and availability of complete genome sequences of Leptospira, development of novel vaccine including recombinant protein vaccine using reverse vaccinology approaches has yielded encouraging results. However, factors hindering the development of effective leptospiral vaccines include variation in serovar distribution from region to region, establishment of renal carrier status following vaccination and determination of the dose and endpoint titres acceptable as definitive indicators of protective immunity. In this review, advancements and progress made in LPS-based vaccines, killed- and live-attenuated vaccines, recombinant peptide vaccines and DNA vaccines against leptospirosis are highlighted.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

Massive intra-alveolar hemorrhage caused by Leptospira serovar Djasiman in a traveler returning from Laos.

Leptospirosis is one of the most common pathogens responsible for life-threatening tropical disease in travelers. We report a case of massive intra-alveolar hemorrhage caused by Leptospira serovar Djasiman in a 38-year-old man returning from Laos, who was cured with antibiotics and salvage treatment with extra-corporeal membrane oxygenation.

Leptospirosis outbreak following severe flooding: a rapid assessment and mass prophylaxis campaign; Guyana, January-February 2005.

BACKGROUND: Leptospirosis is a zoonosis usually transmitted through contact with water or soil contaminated with urine from infected animals. Severe flooding can put individuals at greater risk for contracting leptospirosis in endemic areas. Rapid testing for the disease and large-scale interventions are necessary to identify and control infection. We describe a leptospirosis outbreak following severe flooding and a mass chemoprophylaxis campaign in Guyana. METHODOLOGY/PRINCIPAL FINDINGS: From January-March 2005, we collected data on suspected leptospirosis hospitalizations and deaths. Laboratory testing included anti-leptospiral dot enzyme immunoassay (DST), immunohistochemistry (IHC) staining, and microscopic agglutination testing (MAT). DST testing was conducted for 105 (44%) of 236 patients; 52 (50%) tested positive. Four (57%) paired serum samples tested by MAT were confirmed leptospirosis. Of 34 total deaths attributed to leptospirosis, postmortem samples from 10 (83%) of 12 patients were positive by IHC. Of 201 patients interviewed, 89% reported direct contact with flood waters. A 3-week doxycycline chemoprophylaxis campaign reached over 280,000 people. CONCLUSIONS: A confirmed leptospirosis outbreak in Guyana occurred after severe flooding, resulting in a massive chemoprophylaxis campaign to try to limit morbidity and mortality.

Leptospirosis.

Leptospirosis has recently been classified as an emerging disease because of large clusters of cases resulting from exposure during recreational activities and natural disasters. In addition to their involvement in the prevention, diagnosis, and treatment of leptospirosis in animals, veterinarians serve an important role in public health by providing guidance and information on risk factors and prevention and control measures.

O imprint como método para detecção de leptospita SSP / The imprint as a method to detect leptospita SSP

Na determinação da eficácia de novas candidatas à vacina para leptospirose, o marcador primário considerado é a mortalidade, e um marcador secundário importante é a indução de uma imunidade estéril. Entretanto, a avaliação da imunidade estéril é dificultada pelo tempo demandado e pela complexidade de métodos como o isolamento pela cultura. Neste estudo, foi avaliado o uso do método do imprint (ou touch preparation) na detecção da presença de leptospiras em tecidos de hamsters infectados com L interrogans sorovar Copenhageni. Comparado com a cultura, o imprint demonstrou igualou melhor detecção de leptospiras em amostras de rim, fígado, pulmão e sangue coletadas após a infecção obtendo uma concordância geral boa (K = 0.61). Além disso, na avaliação de hamsters imunizados com uma proteína recombinante de Leptospira candidata à vacina e subsequente desafio com leptospiras patogênicas, a concordância entre a cultura e o imprint foi alta (K = 0.84). Estes achados indicam que o imprint é um método rápido para a observação direta de Leptospira spp. e que pode ser facilmente aplicado na avaliação de animais infectados experimentalmente com leptospiras e na determinação de imunidade esterilizante durante avaliações de potenciais candidatas à vacina.

In determining the efficacy of new vaccine candidates for leptospirosis the primaryendpoint is death and an important secondary endpoint is sterilizing immunity.However, evaluation of this endpoint is often hampered by the time consumingdemands and complexity of methods such as culture isolation (CI). In this study, weevaluated the use of an imprint (or touch preparation) method (IM) in detecting thepresence of leptospires in tissues of hamsters infected with L. interrogans serovar Copenhageni. Compared to CI, the IM exhibited equal or improved detection of leptospires in kidney, liver, lung and blood samples collected post-infection and the overall concordance was good (ê = 0.61). Furthermore, in an evaluation of hamsters immunized with a recombinant Leptospira protein-based vaccine candidate and subsequently challenged with leptospires, the agreement between the CI and IM wasvery good (ê = 0.84). These finding indicate that the IM is a rapid method for the direct observation of Leptospira spp. that can be readily applied to evaluatingLeptospira infection in experimental animals and determining sterilizing immunity when screening potential vaccine candidates.

Optimal treatment of leptospirosis: queries and projections.

Although the global burden of leptospirosis remains enormous and new aspects of the disease are constantly recognised, little progress has been achieved in the field of leptospirosis therapeutics and queries regarding the utility of antibiotics in the late severe form of the disease remain. From the currently existing data, conclusions on the efficacy of antibiotic administration in severe or late disease cannot easily be drawn, since clinical trials have different selection criteria and may focus on Leptospira serovars with different virulence. However, as a rule the benefit of the doubt should apply. Moreover, new options, such as ceftriaxone, have a superior safety profile to penicillin. In vitro studies have outlined potential antimicrobial candidates such as macrolides and ketolides. Development of a globally accepted subunit vaccine for humans is warranted but is not expected in the near future.

Clinical application of a polymerase chain reaction assay for diagnosis of leptospirosis in dogs.

OBJECTIVE: To evaluate the use of a polymerase chain reaction (PCR) assay on urine samples for diagnosis of leptospirosis in dogs. DESIGN: Prospective case study. ANIMALS: 132 dogs with clinical signs suggestive of leptospirosis and 13 healthy dogs. PROCEDURE: PCR testing was performed on urine samples to detect leptospiral DNA; results were compared with results of conventional criteria for the diagnosis of leptospirosis. RESULTS: Leptospirosis was diagnosed in 8 dogs via established criteria; all these dogs had positive results of PCR assay, including 1 dog with positive results before seroconversion developed. A positive PCR assay result was also obtained in 16 dogs that did not have a confirmed diagnosis of leptospirosis. In the 8 dogs that had a confirmed diagnosis of leptospirosis, serovars pomona (n = 3 dogs), grippotyphosa (2), canicola (2), and bratislava (1) were identified serologically. The remaining 121 dogs all had a diagnosis other than leptospirosis or were healthy. For PCR testing on urine, sensitivity was 100%, specificity was 88.3%, positive predictive value was 33%, and negative predictive value was 100%. CONCLUSIONS AND CLINICAL RELEVANCE: Positive PCR test results prior to seroconversion may have value in establishing an early diagnosis. Positive results in dogs that had signs consistent with leptospirosis despite failing to meet established criteria for leptospirosis raise questions regarding the sensitivity of serologic testing in diagnosis of leptospirosis. Serovars pomona, grippotyphosa, and canicola were most common.

Hematoma subdural intracraneal bilateral en un paciente con leptospirosis / Bilateral intracranial subdural hematoma in a patient with leptospirosis

Presentamos el caso de un varón de 39 años de edad, que en el curso de una leptospirosis grave, con fracaso renal agudo, edema agudo de pulmón e ictericia importante, comienza con manifestaciones clínicas de afección neurológica (cefalea, disartria y paresia de la extremidad superior derecha). Se evidencian en tomografía computarizada (TC) y resonancia magnética (RM) hematomas subdurales múltiples y bilaterales. Leptospira puede producir una vasculitis difusa con lesión capilar, dando lugar a distintas manifestaciones hemorrágicas, concretamente en el sistema nervioso es una causa conocida de hemorragia subaracnoidea; el hematoma subdural intracraneal representa un hallazgo no descrito en la bibliografía revisada (AU)

Leptospirosis hemorrágica pulmonar / Hemorrhagic pulmonary leptospirosis

La leptospirosis es una enfermedad infecciosa característica de países orientales húmedos. La incidencia en países occidentales es relativamente infrecuente. La enfermedad suele manifestarse de dos formas clínicas principales: la hepato-renal y la pulmonar, generalmente con cierto grado de solapamiento entre ambas.Presentamos un paciente con una presentación severa de leptospirosis hemorrágica pulmonar que en el curso de la enfermedad, presentó un cuadro de embolismo multisistémico (bazo, riñón y sistema nervioso central -SNC-). (AU)