Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

Successful treatment with streptomycin of genital leptospirosis in naturally infected cows under field conditions.

The single-dose protocol of streptomycin treatment has been recommended to treat renal leptospirosis in bovines. However, treating genital infection remains a challenge. Recently, a protocol using three doses of streptomycin demonstrated effectiveness in the genital clearance of experimentally infected ewes. Therefore, the present study aimed to apply this three-dose protocol for genital infection treatment in naturally infected cows under field conditions. Thirty beef cows were diagnosed as positive by lipL32-PCR in their genital samples. Nucleotide sequences (n = 10) characterized them as Leptospira interrogans sg Sejroe, genetically related to Hardjoprajitno strains. After molecular diagnosis, 13 cows received a single dose of 25 mg/kg streptomycin. The other 17 cows were submitted to the three-dose protocol. The successful treatment rate of genital infection on the single streptomycin dose was 7/13 (53.8%), while the cows that received the three doses 16/17 were negative (94.1% of efficacy). Based on those results, we conclude that the standard treatment preconized for renal infection is not adequate for genital infection, and the three-dose protocol was successful in eliminating the carrier status of genital leptospirosis.

Streptomycin treatment of genital carriers of Leptospira in experimentally infected sheep on different estrous phases.

Leptospirosis in ruminants presents as a chronic disease that causes several reproductive disorders leading to severe economic losses. The current recommended treatment can be efficient to eliminate the renal carrier state, however little is known about the effect of this drug in removing the genital carrier state and the hormonal influence on it. A total of 12 primiparous sheep experimentally infected with a strain of Leptospira santarosai serogroup Sejroe, FV52 strain, were used and distributed as group A (estrus; n = 5), group B (metaestrus; n = 4) and group C (control; n = 3). At D0, groups A and B were treated with streptomycin (25 mg/kg) single dose. Samples of cervicovaginal mucus (CVM) were collected on days 0, 3, and 35 post-treatment, while uterine fragment (UF) samples were collected on days 3 and 35, for PCR. Even after antibiotic treatment, all groups presented infected animals, at D3 and D35, with no significant difference between the treated and control groups. Based on these results, it was conducted a second protocol of treatment with streptomycin, IM (25 mg/kg) for three consecutive days, which was 100% effective to eliminate the genital carrier state; therefore, that protocol should be recommended.

Clinical disease and treatment of Leptospira kirschneri sv Grippotyphosa in a Sumatran tiger (Panthera tigris sumatrae).

CASE DESCRIPTION: A 12-year-old sexually intact male zoo-managed Sumatran tiger (Panthera tigris sumatrae) was evaluated for a 3-day history of vomiting, hyporexia, and lethargy. Radiographs were supportive of gastrointestinal obstruction, and an exploratory laparotomy was performed. CLINICAL FINDINGS: Diffuse tan foci were present on the liver parenchyma, and the tiger became icteric throughout the procedure. Hepatic histopathology and immunohistochemistry resulted in a diagnosis of leptospirosis. Serum microagglutination testing for Leptospira spp antibody titers were positive for L kirschneri serovar Grippotyphosa, rising from 1:400 to 1:3,200 in 2 days. TREATMENT AND OUTCOME: The tiger was treated with antimicrobials, ursodiol, and mirtazapine, and increased biosecurity measures were instituted. Free-ranging wildlife on grounds were trapped, euthanized, and submitted for necropsy to screen for disease vectors. The tiger's urine was intermittently opportunistically collected from the enclosure and remained PCR assay negative for Leptospira spp until being positive once again on day 595. Although the tiger was without clinical signs at that time, antimicrobial therapy and increased biosecurity protocols were instituted a second time until urinary Leptospira shedding was confirmed to have stopped. By 1,071 days after initial presentation, the tiger remained nonclinical, with no additional urinary shedding episodes. CLINICAL RELEVANCE: While domestic and nondomestic free-ranging felids have been reported as subclinical Leptospira spp carriers, this report indicates the clinical importance of leptospirosis when a tiger presents with generalized gastrointestinal signs and icterus. Due to the zoonotic potential, biosecurity measures are necessary. This patient had a clinically successful outcome with antimicrobial therapy and supportive care.

Leptospirosis, una zoonosis que impacta a la salud: diagnóstico, tratamiento y nuevas alternativas de control / Leptospirosis a zoonosis that impacts health: diagnosis, treatment and new alternatives of control

La leptospirosis es una zoonosis con potencial epidémico y de difícil diagnóstico que requiere un manejo integral para orientar las medidas de prevención y control; sin embargo, una de las dificultades es la existencia de más de 300 serovares, la supervivencia de la bacteria en el ambiente por más de 180 días y la importancia del agua como vehículo de transmisión. Esto asociado con los efectos adversos de los antibióticos y su efecto sobre la multirresistencia generada por la mayoría de las bacterias, hace que se evalúen nuevas alternativas a partir de la biodiversidad. Por lo tanto, el objetivo de este artículo es abordar la leptospirosis y su diagnóstico enfatizando en el control convencional de la infección y las alternativas de tratamiento a partir del uso de plantas medicinales. Para esto se realizó una revisión exhaustiva de artículos en bases de datos. La información encontrada permitió establecer los aspectos relevantes de la enfermedad, su diagnóstico y tratamiento, tanto con antimicrobianos convencionales como frente a nuevas alternativas de origen natural. Se concluye que es importante realizar investigaciones orientadas hacia la búsqueda de principios activos que puedan contribuir al control de Leptospira spp., agente causal de la leptospirosis, una de las zoonosis más importantes por su impacto en salud humana, veterinaria y del ecosistema(AU)

Leptospirosis is a potentially epidemic zoonosis of difficult diagnosis which requires comprehensive management to indicate appropriate prevention and control measures. However, some of the difficulties are the existence of more than 300 serovars, survival of the bacteria in the environment for more than 180 days, and the role of water as a route of transmission. The above situation, alongside the adverse effects of antibiotics and their effect on the multi-drug resistance developed by most bacteria, lead to the search for new alternatives based on biodiversity. The purpose of the study was therefore to address leptospirosis and its diagnosis highlighting conventional control of the infection as well as treatment options based on the use of medicinal plants. To achieve this end, an exhaustive review was conducted of papers included in databases. The information obtained made it possible to determine the relevant aspects of the disease, its diagnosis and its treatment with conventional antimicrobials as well as new alternatives of a natural origin. Conclusions point to the importance of conducting research aimed at the search for active principles potentially contributing to control of Leptospira spp., the causative agent of leptospirosis, one of the most relevant zoonoses in terms of its impact on the health of humans, animals and the ecosystem(AU)

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.

Identifying factors associated with treatment delay in leptospirosis: A retrospective study of patients admitted to hospital in Reunion (Indian Ocean) between 2014 and 2015.

BACKGROUND: Leptospirosis is a life-threatening zoonotic disease for which delayed treatment onset has been associated to poor prognosis. The purpose of the study was to identify the determinants of therapeutic delay in hospitalized leptospirosis cases. PATIENTS AND METHODS: We carried out a retrospective multicenter study in the 4 public hospitals of Reunion Island, South Western Indian Ocean. Medical records of confirmed leptospirosis cases occurring in 2014-2015 were reviewed for socio-economic, demographic, geographic and medical data. The primary outcome measure was the therapeutic delay, defined as the time elapsed between the onset of symptoms and initiation of antibiotics. RESULTS: Of the 117 patients included, 107 were men, with an average age of 44.9±15years. The median therapeutic delay was 4 days (interquartile: 2-5 days) and this delay was not found to be associated with severity. The following were found to be at increased risk of having a longer therapeutic delay: cases occurring outside the epidemic period, or rainy season (OR 2.8 [1.08-7.3], P=0.04) and cases with first medical evaluation in primary health care (OR 4.63 [1.43-14.93]; P=0.01) instead of emergency unit. No socio-economic or geographic characteristics were found to be linked to a longer therapeutic delay. CONCLUSION: Although delayed treatment was not associated to disease severity, our results indicate that leptospirosis awareness is needed all year in the subtropical area of Reunion Island and particularly in primary care.

Persistent Leptospiruria in Five Dogs Despite Antimicrobial Treatment (2000-2017).

In dogs with leptospirosis, doxycycline therapy is recommended as the preferred therapy for its ability to eliminate the organism from all tissues, including the renal tubules. Elimination of organisms from the renal tubules terminates leptospiruria and prevents transmission of the organism. This report describes the discovery of persistent leptospiruria in the face of therapy with doxycycline in four dogs and enrofloxacin in one dog. Leptospiruria was confirmed by polymerase chain reaction testing for pathogenic leptospires in all five dogs. In two dogs, leptospiruria resolved after a change in therapy to enrofloxacin. In three dogs, doxycycline and/or enrofloxacin were ineffective at eliminating leptospiruria, which then resolved after therapy with clarithromycin. Pet owners could be at risk as persistent leptospiruria poses a potential zoonotic risk. The potential reasons for persistent leptospiruria as demonstrated by polymerase chain reaction testing are discussed.

Leptospirosis following heavy rains in 2017 in Mumbai: Report of large-scale community chemoprophylaxis.

Background: Globally, cities get flooded due to heavy rains. As the incidence of leptospirosis increases after such flooding in Mumbai, community chemoprophylaxis to selected individuals was a consensus recommendation by experts. Methods: We surveyed a total of 1 499 293 houses in severely affected areas of Mumbai (where there was waterlogging or high incidence of leptospirosis in the past) as well as in all slum areas. A total of 6 714 210 people (>50% of the population) were screened. A total of 156 934 adults, 4465 children, 359 pregnant women and 4957 high-risk adults were given prophylaxis with doxycycline or azithromycin by paramedical staff (n = 9526) under the supervision of medical staff. Social media and newspaper advertisements were used to create public awareness. Results: Compared with previous floods, there were reduced number of cases of leptospirosis due to community chemoprophylaxis (432 confirmed cases in 2005 v. 128 [59 confirmed] in 2017). Conclusions: Selective, time-bound chemoprophylaxis following floods is likely to reduce the incidence of leptospirosis, as well as associated morbidity and mortality.

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.

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.

Effect of Antimicrobial Agents on Inflammatory Cytokines in Acute Leptospirosis.

The aim of this study was to assess the inflammatory cytokine response and possible association with antimicrobial treatment with penicillin, ceftriaxone, and doxycycline in acute leptospirosis. In the early acute stage, interleukin-10 (IL-10) levels were higher in mild cases than in severe cases (P = 0.01). IL-6 and IL-8 levels were low in patients who received >5 antimicrobial doses (P < 0.01). IL-8 levels were negatively correlated with the number of ceftriaxone doses administered (r = -0.315; P = 0.031). Further studies are needed to evaluate the possible downregulation of proinflammatory cytokines by ceftriaxone in leptospirosis.

La importancia de interrogar el trabajo del paciente: a propósito de un caso de leptospirosis / Report of a case of leptospirosis: the importance of asking the patient about workplace factors

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Leptospirosis in three workers on a dairy farm with unvaccinated cattle.

AIM: We report a one-health investigation of three cases of leptospirosis on a dairy farm with unvaccinated cattle in New Zealand. The cases are discussed in the context of diagnostics, risk factors, persistence of symptoms and outbreak mitigation measures. METHOD: Clinical and laboratory records from the human cases were reviewed and serological and molecular investigations were conducted into the Leptospira status of cattle and pigs on the farm. RESULTS: Cases presented early in their illness and all three were confirmed within seven days of onset of symptoms by urine PCR and within 18 days by convalescent MAT (two Hardjo, one Pomona). Cattle and pigs had serological evidence of recent infection with Hardjo/Pomona and Pomona/Copenhageni respectively. Pigs were slaughtered and cattle were vaccinated. Post-exposure prophylaxis was given to staff in-contact with the milking herd until the herd had antibiotic treatment at drying-off (approximately four months after the initial case). CONCLUSION: The utility of PCR testing for Leptospira DNA as both an early and rapid test for leptospirosis was demonstrated. Two of three cases reported persistence of symptoms at least six months after the acute episode and one of these remains unable to work. Risk mitigation measures such as post-exposure prophylaxis, animal vaccination, heightened clinical suspicion of leptospirosis and recognition of context specific risk factors (eg, effluent spreading) demonstrate the value of medical and veterinary experts working together.

Comparing antibiotic treatment for leptospirosis using network meta-analysis: a tutorial.

BACKGROUND: Network meta-analysis consists of simultaneous analysis of both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator. In this paper, we aimed to characterise the conceptual understanding and the rationale for the use of network meta-analysis in assessing drug efficacy. METHODS: We selected randomized controlled trials, assessing efficacy of antibiotics for the treatment of leptospirosis as a case study. A pairwise meta-analysis was conducted using a random effect model, assuming that different studies assessed different but related treatment effects. The analysis was then extended to a network meta-analysis, which consists of direct and indirect evidence in a network of antibiotics trials, using a suite of multivariate meta-analysis routines of STATA (mvmeta command). We also assessed an assumption of 'consistency' that estimates of treatment effects from direct and indirect evidence are in agreement. RESULTS: Seven randomised controlled trials were identified for this analysis. These RCTs assessed the efficacy of antibiotics such as penicillin, doxycycline and cephalosporin for the treatment of human leptospirosis. These studies made comparisons between antibiotics (i.e. an antibiotic versus alternative antibiotic) in the primary study and a placebo, except for cephalosporin. These studies were sufficient to allow the creation of a network for the network meta-analysis; a closed loop in which three comparator antibiotics were connected to each other through a polygon. The comparison of penicillin versus the placebo has the largest contribution to the entire network (31.8%). The assessment of rank probabilities indicated that penicillin presented the greatest likelihood of improving efficacy among the evaluated antibiotics for treating leptospirosis. CONCLUSIONS: Findings suggest that network meta-analysis, a meta-analysis comparing multiple treatments, is feasible and should be considered as better precision of effect estimates for decisions when several antibiotic options are available for the treatment of leptospirosis.

Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster.

Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1ß and TNF-α was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1ß and TNF-α was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis.

Different clinical spectrum of leptospirosis.

Leptospirosis is a prevalent zoonotic disease. Human infection usually occurs through exposure to environmental sources. Clinical course of leptospirosis is variable. We presented five patients, aged between 4-14 years, having a history of contact with rodents and symptoms 7-10 days after contact. The first three cases were relatives and had contact with dead rats after applying insecticides to bakery across from their house. The first case diagnosed as isolated meningitis, others as flu-like illness. The fourth case had a contact history with a rat inundate in the canalization and diagnosed as acute hepatitis. The last case, living in a village with poor sanitation, developed secondary hemophagocytic syndrome. ELISA was performed for diagnosis. High dose penicillin and additional immunosuppressive drugs for the last case were used. All cases showed recovery within 10 days. Leptospirosis should be considered in any patient presenting with an abrupt onset or prolonged fever, myalgia, headache and jaundice.

A case-control study of epidemiological factors associated with leptospirosis in South Gujarat region.

BACKGROUND: The current study was planned to identify the epidemiological factors associated with leptospirosis in South Gujarat region using neighborhood controls. METHODS: A total of 100 cases of leptospirosis occurred in South Gujarat region during the year 2012 were selected using simple random sampling. Three neighbors of the selected cases formed the controls (n = 300). A pretested structured questionnaire was used for data collection and data were analyzed using Epi Info 2007. RESULTS: There was significant association of illiteracy (odds ratio [OR] =1.82, 95% confidence interval [CI] =1.14-2.89), working in waterlogged fields during the reference season (OR = 4.6, 95% CI = 1.6-17.9), swimming/bathing in canals, open air defecation practices, storage of cow dung in or surrounding house, residence in the house made up of cow dung walls, households with access of food to rodents, injuries over hands/foot during the endemic season (OR = 3, 95% CI = 1.8-4.8), and history of skin disease during the endemic season (OR = 4.2, 95% CI = 2-8.5), with leptospirosis. Only 10% of individuals had gumboots for protection. A total of 83 (83%) cases and 240 (80%) controls had taken oral doxycycline chemoprophylaxis (P > 0.05). Cases had taken chemoprophylaxis for a median 4 weeks (range: 1-8) while controls had taken the same for median 8 weeks (range = 1-8) (P < 0.002). CONCLUSIONS: Although the commonly established factors appear to be associated with leptospirosis, the role of host factors seems to play a more important role in determining susceptibility to leptospirosis in exposed individuals.

[A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis.