Key messages
- There is insufficient data to know the potential benefits and harms of corticosteroids compared with no treatment, no treatment beyond the standard of care, or placebo (a dummy medicine) in the treatment of people with leptospirosis infection.
- Corticosteroids may decrease transient inflammatory reaction events associated with antibiotic treatment of leptospirosis infection, although the certainty of this evidence is very uncertain.
- Data from more rigorously conducted clinical trials is required to evaluate the most appropriate treatments for leptospirosis.
What is leptospirosis?
Leptospirosis is an infectious disease found worldwide. It is transmitted to humans through contact with water, soil, or food, containing the urine of infected animals. While many people with the infection show mild flu-like symptoms that resolve on their own and usually do not require medical attention, some may develop a severe form of the illness, leading to malfunction in multiple organs which, in some cases, can lead to death.
How is leptospirosis treated?
Early antibiotics and targeted organ support strategies are the main interventions for the treatment of leptospirosis. Corticosteroids have been used to treat leptospirosis, particularly in severe manifestations of the disease. However, the effectiveness of corticosteroids as a direct or complimentary treatment for leptospirosis is not well understood.
We wanted to know:
- Can corticosteroids be an effective treatment for leptospirosis?
- Can treatment with corticosteroids cause unwanted adverse events (serious and minor)?
- Can treatment with corticosteroids reduce the length of hospitalisation due to leptospirosis?
- Can treatment with corticosteroids reduce inflammatory reactions that can or are likely to cause a life-threatening drop in blood pressure, swelling or pain when people are treated for leptospirosis?
- Can corticosteroids improve health-related quality of life?
What did we do?
We searched medical databases for randomised clinical trials, which are studies where participants are allocated at random to groups, to find out which treatment is best. In our review, the studies we have included compared a corticosteroid drug (alone or in combination) against no intervention, no intervention beyond standard of care, or a placebo (i.e. sham treatment) treatment of people with leptospirosis.
What did we find?
We found four randomised clinical trials with a total of 253 participants, conducted in countries where leptospirosis is a major public health issue (Thailand, Brazil, China, and Iran). The participants resided in these areas. All studies were judged to be at some concern or high risk of bias.
What are the main results of our review?
One trial compared prednisolone against a placebo. One trial compared both dexamethasone and prednisolone against no intervention beyond the standard of care. One trial compared methylprednisolone against no intervention beyond the standard of care. One trial compared hydrocortisone against no intervention. The three trials reporting standard of care administered co-interventions in a similar way and included either supportive management or antimicrobial treatment.
We do not know if corticosteroids, compared to no intervention beyond standard of care or placebo treatment, decrease the risk of death in those with leptospirosis (3 studies, 123 participants); decrease the number of people experiencing serious unwanted events (3 studies, 123 participants); or reduce the number of days spent in a hospital due to leptospirosis (3 studies, 123 participants), as the evidence is very uncertain. Similarly, we do not know if corticosteroids, compared to no intervention beyond standard of care, decrease the risk of non-serious unwanted events (1 study, 22 participants) as the evidence is very uncertain. Finally, we do not know if corticosteroids, compared with no intervention, decrease short-term inflammatory reactions associated with leptospirosis antibiotic treatment (1 trial, 130 participants) as the evidence is also very uncertain.
None of these trials assessed quality of life.
What are the limitations of the evidence?
Because of the very low certainty of the evidence in the four trials, we are not confident about these results. Our findings were based on a few studies, with differing study outcomes, challenges in the selection and randomisation of participants, insufficient overall participants in the studies, and conflicting results between studies for some recorded outcomes.
Funding
Two studies included statements disclosing their funding sources, and the remaining two did not. Of the studies disclosing their funding, one received financial support from a university but made no further disclosure. The other study disclosed that they had received funding from both governmental and international charitable organisations, but that these sources were not involved in the design, conduct, analysis, or reporting of study results.
How up-to-date is this evidence?
This evidence is up-to-date as of 10 April 2025.
阅读完整摘要
Leptospirosis is a bacterial disease caused by Leptospira spp, a zoonotic pathogen spread via contaminated soil and water. Corticosteroids have been used for the treatment or prevention of severe manifestations of disease, but the indications for their use and treatment efficacy remain uncertain. This review evaluates the existing evidence for the use of corticosteroids in leptospirosis from randomised trials.
研究目的
To assess the benefits and harms of corticosteroids versus no intervention, no intervention beyond standard of care, or placebo for the treatment of people with leptospirosis.
检索策略
Electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index – Science, and other resources were conducted. We searched online clinical trial registries to identify unpublished or ongoing trials, and reviewed reference lists from the identified publications for potential trials. We contacted authors of identified trials, relevant individuals, and organisations for additional information. The last search date was 10 April 2025.
纳入排除标准
We considered the inclusion of randomised clinical trials of any trial design which assessed corticosteroids for the treatment of leptospirosis. We imposed no restrictions on age, sex, occupation, comorbidity of trial participants, or outcomes reported. We looked for trials assessing corticosteroids irrespective of type, route of administration, dosage, and schedule versus no intervention, placebo, or no intervention beyond standard care. We included trials meeting any of these criteria, irrespective of the manuscript’s primary language.
资料收集与分析
We adhered to Cochrane methodology. Data entry and analysis were facilitated by the use of the Review Manager. The primary outcomes were all-cause mortality and the proportion of individuals experiencing serious adverse events. The secondary outcomes were quality of life, the proportion of individuals experiencing non-serious adverse events, days of hospitalisation, and the proportion of individuals experiencing Jarisch-Herxheimer reactions.
We employed the risk of bias 2 tool (RoB 2) to assess the bias risk of included trials. We used the GRADEPro software to evaluate the certainty of evidence. 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 applied a random-effects meta-analysis for the primary analysis and a fixed-effect model for the sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. We analysed the outcome data regardless of the risk of bias.
主要结果
Four randomised trials were included in this review, with a pooled total of 253 participants. Each of the trials compared a corticosteroid (prednisolone, hydrocortisone, a combined treatment regimen of dexamethasone and prednisolone, or methylprednisolone) versus no intervention, no intervention beyond standard of care, or placebo. Participants in three trials received similarly administered co-interventions as standard of care, and had no further intervention in the fourth trial. All participants were recruited from populations presenting to general hospitals in leptospirosis endemic settings. The ages of the participants ranged from six years to 65 years. Depending on the trial, the treatment duration ranged from over four hours to seven days.
All included trials were judged to have either some concerns or to be at high risk of bias. The certainty of evidence for all evaluated outcomes was judged to be very low. Quality of evidence was downgraded for risk of bias arising from the randomisation process, measurement of outcome, and selection of reporting of results; indirectness of evidence due to choice of intervention; inconsistency due to different point estimates and unexplained heterogeneity; and imprecision attributable to confidence intervals (CI) crossing clinically important thresholds, failure to meet optimal information size, or an upper/lower CI boundary more than three risk ratios.
Corticosteroids compared with no intervention beyond standard of care or placebo may have little to no effect on all-cause mortality (RR 1.04, 95% CI 0.38 to 2.80, I2 = 0%, 3 trials, 123 participants, very low-certainty evidence) and on the proportion of individuals experiencing serious adverse events (RR 1.15, 95% CI 0.32 to 4.11, I2 = 62%, 3 trials, 123 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may increase the proportion of individuals experiencing non-serious adverse events (RR 2.00, 95% CI 0.21 to 18.98, 1 trial, 22 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may decrease the number of days of hospitalisation (MD 0.46, 95% CI -1.81 to 2.73, I2 = 83%, 3 trials, 123 participants, very low-certainty of evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention may reduce the risk of Jarisch-Herxheimer reaction events (RR 0.13, 95% CI 0.04 to 0.41, 1 trial, 130 participants, very low-certainty evidence), but the evidence is very uncertain.
None of the four trials assessed health-related quality of life.
We have listed one trial registered as 'randomised' in studies awaiting classification because we could not identify further information. We have listed one trial in the ongoing section because trial recruitment has not yet started.
作者结论
Based on the very low certainty of evidence attributable to our analyses, we do not know whether corticosteroids compared with no intervention, no intervention beyond standard of care, or placebo, reduce all-cause mortality, increase the risk of serious or non-serious adverse events, decrease days of hospitalisation, or decrease the proportion of people experiencing Jarisch–Herxheimer reaction events. None of the four trials assessed health-related quality of life.
There is a lack of harmonised treatment strategies, clinically relevant outcome definitions, and definitive and rigorously designed randomised trials to support the use of corticosteroids for leptospirosis. Future research should focus on these evidence gaps.
